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Buhari et al
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IAA Journal of Biological Sciences 11(1):12-32, 2023. ISSN:2636-7254
©IAAJOURNALS
https://doi.org/10.59298/IAAJB/2023/2.2.23310
12
Advancements in Myeloid Leukemia Treatment: A Comprehensive
Update
Hauwa Ali Buhari1, Salisu, Muhammad1 and *Emmanuel Ifeanyi Obeagu2
1Department of Haematology, School of Medical Laboratory Sciences, Usmanu
Danfodiyo University, Sokoto, Nigeria.
2Department of Medical Laboratory Science, Kampala International University,
Uganda.
*Corresponding author: Emmanuel Ifeanyi Obeagu, Department of Medical
Laboratory Science, Kampala International University, Uganda.
emmanuelobeagu@yahoo.com, obeagu.emmanuel@kiu.ac.ug 0000-0002-4538-
0161
ABSTRACT
This comprehensive update explores the recent advancements in the treatment
landscape of myeloid leukemia. Myeloid leukemia, a heterogeneous group of
hematological malignancies, poses significant challenges in clinical management.
This review highlights the latest therapeutic approaches, including targeted
therapies, immunotherapies, and emerging treatment modalities. It discusses the
impact of precision medicine, novel drug developments, and the evolving role of
immunotherapy in managing myeloid leukemia. Furthermore, the abstract outlines
current research trends, challenges, and future prospects, aiming to provide a
concise overview for healthcare professionals and researchers involved in leukemia
management.
Keywords: targeted therapy; immunotherapy; precision medicine; molecular
profiling; personalized treatment; bone marrow transplantation; novel therapies
INTRODUCTION
Myeloid leukemia is a type of cancer
that affects the myeloid cells in the
bone marrow. It is characterized by
the abnormal growth and
accumulation of immature myeloid
cells, which can interfere with the
production of normal blood cells [1-3].
The classification and management of
myeloid leukemia have been updated
in recent years to improve diagnosis,
risk stratification, and treatment. The
International Consensus Classification
(ICC) and the 5th edition of the WHO
classification are two competing
schemata that emerged in 2022.
Research on myeloid leukemia has
also focused on understanding the
genetic and molecular mechanisms
underlying the disease. For example,
studies have explored the role of
specific genes and mutations in the
development and progression of
myeloid leukemia. These findings
have contributed to the development
of targeted therapies that aim to
inhibit the abnormal signaling
pathways involved in leukemia cells
[4-6]. In the past few decades, progress
in hematopoietic malignancy
treatment has been especially rapid
due to improvements in treatment
protocols, including the development
of targeted therapies such as tyrosine
kinase inhibitors (TKIs). However, the
current outlook for leukemia is not
optimistic, and it is still a major threat
to human health. In 2020, leukemia
was estimated to be the 15th and 11th
most frequent cause of cancer
incidence and cancer-related mortality
worldwide, respectively, accounting
for 474,519 incident cases and
311,594 deaths. In addition, leukemia
is the most common cancer in children
younger than five years of age and
accounts for the highest percentage of
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13
deaths, creating a significant burden
on individuals, families, and countries
[7-9].
Importance of understanding latest updates on myeloid leukemia
Staying updated on the latest
developments and research in myeloid
leukemia is crucial for several reasons.
Firstly, understanding the latest
updates on myeloid leukemia allows
healthcare professionals to provide
the most effective and personalized
treatment options for patients. The
role of next-generation sequencing
(NGS) in acute myeloid leukemia (AML)
has been highlighted as a valuable tool
for identifying relevant genetic
entities [10-12]. NGS can help identify
specific mutations and genetic
abnormalities in AML, which can guide
treatment decisions and improve
patient outcomes. Secondly, staying
informed about the latest updates on
myeloid leukemia is important for
researchers and scientists working in
the field. Molecular findings in
myeloid neoplasms continue to
evolve, and understanding these
findings can help drive further
research and advancements in the
field [13]. By keeping up with the latest
research, scientists can identify new
targets for therapy, develop novel
treatment approaches, and improve
our overall understanding of the
disease. Lastly, being aware of the
latest updates on myeloid leukemia is
important for patients and their
families. Cancer statistics for 2023
show that mortality rates for leukemia
have been declining, indicating
progress in treatment options [14].
Patients and their families can benefit
from knowing about the latest
advancements in treatment, as it can
provide hope and reassurance. It also
allows them to have informed
discussions with their healthcare
providers and actively participates in
their treatment decisions.
Subtypes of acute leukemia and their characteristics
Acute myeloid leukemia (AML) is a
heterogeneous disease with various
subtypes, each characterized by
distinct genetic and clinical features.
The classification of AML subtypes has
evolved over time, with different
classification systems used in the
past. The French-American-British
(FAB) classification, developed in the
1970s, divided AML into subtypes
based on the type of cell from which
the leukemia develops and the
maturity of the cells [15-17]. However,
the FAB classification is no longer
used in clinical practice. The World
Health Organization (WHO)
classification is currently the most
widely accepted classification system
for AML. The WHO classification takes
into account not only morphological
features but also genetic and
molecular abnormalities [18].
According to the WHO classification,
AML is divided into several subtypes,
including acute promyelocytic
leukemia (APL), acute erythroid
leukemia (AEL), acute megakaryocytic
leukemia (AMKL), and others.APL is a
distinct subtype of AML characterized
by the presence of the PML-RARA
fusion gene resulting from the t(15;17)
translocation [19-21]. APL is
associated with a favorable prognosis
and is treated differently from other
subtypes of AML [19]. AEL is a rare
subtype of AML characterized by
prominent erythroid proliferation
[22]. AMKL is characterized by the
unrestricted proliferation of immature
megakaryocytes (megakaryoblasts)
and extensive myelofibrosis [23]. In
addition to these subtypes, AML can be
further classified based on specific
genetic abnormalities. For example,
mutations in the TP53 gene and RB1
gene have been associated with poor
prognosis in pediatric AML. Mutations
in the FLT3 gene are also common in
AML and are associated with a poor
prognosis). Other genetic
abnormalities, such as amplification
of the EPOR/JAK2 genes, have been
identified in specific subtypes of AML
[22, 24-25]. It is important to note that
the classification of AML subtypes is
constantly evolving as new research
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uncovers additional genetic and
molecular abnormalities associated
with the disease. The identification of
these subtypes is crucial for guiding
treatment decisions and predicting
prognosis in patients with AML.
Recent advances in the treatment of acute myeloid leukemia
Recent advances in the treatment of
Acute Myeloid Leukemia (AML) have
focused on various aspects of the
disease, including targeted therapies,
immunotherapy, precision medicine,
and the identification of novel
therapeutic targets. Despite these
advances, achieving long-term
disease-free survival in AML remains a
challenge. One area of research that
has shown promise in AML treatment
is the use of chimeric antigen receptor
(CAR) T cell therapy. CAR T cell
therapy involves modifying a patient's
own T cells to express a receptor that
recognizes and targets specific
antigens on cancer cells. In the case of
AML, CAR T cell therapy has shown
excellent results in acute lymphocytic
leukemia (ALL) and lymphoma, and
there is potential for its use in AML as
well [26-28]. Another area of research
is the identification of genetic
mutations in AML that can be targeted
with precision medicine. Mutations in
genes such as IDH1/2 have been
identified in AML and have become
targets for precision medicine
approaches [29]. Additionally,
pharmacogenomic profiling has been
used to identify therapeutic
vulnerabilities in pediatric AML, which
can inform personalized treatment
strategies [30]. The use of targeted
therapies, such as venetoclax, has also
shown promise in the treatment of
relapsed/refractory AML. Venetoclax,
in combination with other agents such
as azacitidine, has achieved
impressive results in newly diagnosed
elderly patients with AML and
refractory/relapsed disease.
Furthermore, the efficacy and safety
of venetoclax for relapsed/refractory
AML have been evaluated through
systematic reviews and meta-analyses
[31]. Immunotherapy has emerged as a
promising approach in AML treatment.
Targeting immune checkpoints, such
as the STAT3-VISTA axis, has shown
potential in suppressing tumor
aggression and burden in AML [32].
Etiology and risk factors
A. Genetic and environmental factors
Genetic and environmental factors
play significant roles in the
development of myeloid leukemia.
Several studies have investigated
these factors and their impact on the
disease. Genetic mutations have been
identified as a key factor in the
development of myeloid leukemia.
The homeobox transcription factors
HoxA9 and Meis1 have been found to
be causally involved in the etiology of
acute myeloid leukemia [33].
Additionally, mutations in genes such
as ASXL1 have been shown to disrupt
the proliferation-differentiation
balance and promote stem-cell
identity over differentiation in
myeloid leukemias. Furthermore,
missense mutations and gene
rearrangements have been associated
with the development of neonatal
congenital leukemia. These findings
highlight the importance of genetic
abnormalities in the pathogenesis of
myeloid leukemia. Environmental
factors also contribute to the
development of myeloid leukemia.
Exposure to radiation, chemicals, and
other occupational hazards has been
implicated in the development of the
disease. Intrauterine exposure to
radiation, drugs, or toxins has been
linked to the occurrence of acute
myeloid leukemia after birth.
Additionally, viral agents have been
identified as potential contributors to
the development of leukemia. These
environmental factors can interact
with genetic mutations to increase the
risk of myeloid leukemia.The
pathogenesis of myeloid leukemia
involves various molecular and
genetic abnormalities.
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B. Hereditary predisposition
Hereditary predisposition can play a
significant role in the development of
myeloid leukemia. Several germline
mutations have been identified that
are associated with an increased risk
of developing myeloid neoplasms,
including acute myeloid leukemia
(AML) and myelodysplastic syndrome
(MDS). These mutations include
RUNX1, CEBPA, GATA2, ANKRD26,
DDX41, and ETV6 mutations. Patients
with these germline mutations may
present with hypocellular MDS at a
young age. Additionally, familial
platelet disorder with associated
myeloid malignancy (FPDMM), caused
by inherited RUNX1 mutations, is
characterized by thrombocytopenia,
platelet activation defects, accelerated
clonal hematopoiesis, and an
increased risk of leukemia [34].
C. Occupation and lifestyle factors
Occupation and lifestyle factors can
play a role in the development of
myeloid leukemia. Several studies
have suggested that certain
occupational and environmental
exposures, as well as lifestyle habits,
may increase the risk of developing
leukemia. These factors can include
exposure to chemicals, such as
pesticides and benzene, as well as
exposure to radiation [35].
Environmental factors, such as
exposure to certain chemicals and
radiation, have also been implicated in
the development of myeloid leukemia.
Exposure to benzene, a chemical
found in various industries, has been
identified as a well-known cause of
adult leukemia, including myeloid
leukemia. Additionally, exposure to
ionizing radiation, such as from
medical imaging procedures like
computed tomography (CT) scans, has
been associated with an increased risk
of developing leukemia, particularly in
childhood and early adulthood.
Diagnosis and staging
Diagnosis and staging of myeloid
leukemia are crucial steps in
determining the appropriate
treatment and prognosis for patients.
Myeloid leukemia refers to a group of
hematological malignancies
characterized by the uncontrolled
proliferation of myeloid cells in the
bone marrow and peripheral blood.
The diagnosis and staging of myeloid
leukemia involve a combination of
clinical evaluation, laboratory tests,
imaging studies, and molecular
analysis. To diagnose myeloid
leukemia, a thorough medical history
and physical examination are
conducted to assess symptoms and
identify potential risk factors. Blood
tests, including complete blood count
(CBC) and peripheral blood smear, are
performed to evaluate the levels and
morphology of blood cells.
Abnormalities in the CBC, such as
leukocytosis, anemia, and
thrombocytopenia, may indicate the
presence of myeloid leukemia [36].
Bone marrow aspiration and biopsy
are essential diagnostic procedures
for myeloid leukemia. These
procedures involve the collection of a
sample of bone marrow cells for
examination under a microscope. The
examination of bone marrow cells
allows for the identification of
abnormal cells, such as blasts, which
are immature cells that have not fully
differentiated into mature blood cells.
The presence of blasts in the bone
marrow is a hallmark of myeloid
leukemia [37]. Immunophenotyping, a
technique that uses flow cytometry, is
often employed to further
characterize the abnormal cells in
myeloid leukemia. This technique
involves the labeling of cells with
specific antibodies that target cell
surface markers. By analyzing the
expression of these markers,
immunophenotyping can help
differentiate between different
subtypes of myeloid leukemia and
determine the lineage of the abnormal
cells [38].
Molecular analysis plays a crucial role
in the diagnosis and classification of
myeloid leukemia. Cytogenetic
analysis, which examines the
chromosomes of cancer cells, can
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identify specific chromosomal
abnormalities that are associated with
different subtypes of myeloid
leukemia. For example, the presence
of the Philadelphia chromosome
(t9;22) is characteristic of chronic
myeloid leukemia (CML) [39].Once a
diagnosis of myeloid leukemia is
established, staging is performed to
determine the extent of the disease
and guide treatment decisions. The
most commonly used staging system
for myeloid leukemia is the French-
American-British (FAB) classification,
which categorizes myeloid leukemia
into different subtypes based on the
morphology and lineage of the
abnormal cells. The World Health
Organization (WHO) classification
system is another widely accepted
classification system that
incorporates cytogenetic and
molecular genetic information to
further refine the classification of
myeloid leukemia [40]. In addition to
the FAB and WHO classification
systems, other factors, such as the
presence of specific gene mutations
and the patient's overall health, are
taken into consideration when staging
myeloid leukemia. For example, the
European LeukemiaNet (ELN) provides
recommendations for risk
stratification in acute myeloid
leukemia (AML) based on cytogenetic
and molecular genetic abnormalities,
as well as the patient's age and
performance status [37].
Symptoms and clinical presentations
Common signs and symptoms
Myeloid leukemia is a type of leukemia
that originates in the myeloid cells,
which are responsible for producing
red blood cells, white blood cells, and
platelets [41]. The clinical symptoms
of myeloid leukemia can vary
depending on the subtype and stage of
the disease. However, there are some
common clinical symptoms that are
often observed in patients with
myeloid leukemia. One of the common
clinical symptoms of myeloid
leukemia is constitutional symptoms,
which include weight loss, fatigue, and
night sweats. These symptoms are
often nonspecific and can be
attributed to various other conditions.
However, in the context of myeloid
leukemia, they are believed to be
caused by the abnormal production
and accumulation of immature
myeloid cells in the bone marrow,
leading to anemia and other systemic
effects [42]. Another common clinical
symptom of myeloid leukemia is
hepatosplenomegaly, which refers to
the enlargement of the liver and
spleen. This is often observed in
patients with advanced stages of the
disease and is caused by the
infiltration of leukemic cells into these
organs [42]. Furthermore, myeloid
leukemia can also present with
cutaneous manifestations, such as
leukemia cutis or myeloid sarcoma.
Leukemia cutis refers to the
infiltration of leukemic cells into the
skin, resulting in the formation of skin
lesions. Myeloid sarcoma, on the other
hand, refers to the formation of solid
masses of leukemic cells outside of
the bone marrow [43]. Other less
common clinical symptoms of myeloid
leukemia include bone pain, osteoid
osteoma, and neurological
manifestations. Bone pain can occur
due to the infiltration of leukemic cells
into the bone marrow, leading to bone
destruction. Osteoid osteoma, which
is a benign bone tumor, has also been
reported in patients with myeloid
leukemia [44].
Complications and disease progressions
Complications and disease
progressions in myeloid leukemia can
have significant impacts on patient
outcomes and treatment strategies.
Myelodysplastic syndromes (MDS) are
a group of clonal hematopoietic stem
cell diseases characterized by
cytopenias and cytopenia-related
complications, such as infections and
bleeding, as well as a high risk of
progression to acute myeloid leukemia
(AML) [45]. Patients suffering from
acute myeloid leukemia are at a
greater risk of acquiring Severe Acute
Respiratory Syndrome Coronavirus 2
(SARS-CoV-2) infection along with
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developing complications related to
COVID-19 due to the
immunosuppression caused by the
malignancy, as well as the high-
intensity chemotherapy provided in
acute myeloid leukemia [46-66].
Therapy-related acute myeloid
leukemia (t-AML) and myelodysplastic
syndrome (t-MDS) are complications of
chemotherapy and/or radiation
therapy for malignant diseasesx.
Acute myeloid leukemia (AML) and
other hematologic malignancies can
be complicated by hyperleukocytosis,
which leads to an increased risk for
other severe complications such as
tumor lysis syndrome, disseminated
intravascular coagulation (DIC), and
leukostasis. Myeloproliferative
neoplasms (MPNs) encompass a
spectrum of disease entities with
progressively more severe clinical
features, including complications with
thrombosis and hemostasis and an
increased propensity for
transformation to acute myeloid
leukemia. Primary causes of death
among MDS patients are complications
due to bone marrow failure (e.g.,
infections, hemorrhage, and platelet
dysfunction) and post-MDS
transformation to secondary acute
myeloid leukemia (sAML) [67].
Current treatment modalities
A. Chemotherapy and targeted therapies
Chemotherapy and targeted therapies
are the primary treatment options for
both acute and chronic myeloid
leukemia. Chemotherapy is commonly
used as the first-line therapy for acute
myeloid leukemia (AML) and has
shown high remission rates [68]. It is
often administered in combination
with other antineoplastic agents to
improve efficacy. However,
chemotherapy can have significant
side effects and impact the patient's
quality of life. Targeted therapies, on
the other hand, specifically target
molecular abnormalities in leukemia
cells, offering a more precise and
potentially less toxic treatment
approach [69]. One targeted therapy
option for myeloidleukemia is the use
of tyrosine kinase inhibitors (TKIs)
that inhibit BCR/ABL tyrosine kinase
activity. TKIs have revolutionized the
treatment and prognosis of chronic
myeloid leukemia (CML) in recent
decades. Another targeted therapy
option is the use of BH3 mimetics,
which are small molecule inhibitors
that target the prosurvival members of
the BCL-2 family. BH3 mimetics have
shown promise in the treatment of
acute myeloid leukemia when used
alone or in combination with standard-
of-care therapies [70].
Immunotherapy, particularly chimeric
antigen receptor (CAR) T-cell therapy,
has also emerged as a potential
treatment option for acute myeloid
leukemia. CAR-T therapies targeting
myeloid-lineage antigens such as
CD123 and CD33 have shown
significant antitumor efficacy.
However, the ideal targets for CAR-T
therapy in AML are still being
investigated. Additionally, T-cell-
based immunotherapy, such as
allogeneic hematopoietic stem cell
transplantation (allo-HSCT), has been a
cornerstone of AML treatment for
decades, offering the potential for
cure in a subset of patients [69].
Chemotherapy is recommended even
with an initial response to radiation,
similar to the treatment of AML.
However, there is no specific
treatment protocol for myeloid
sarcoma, and the same treatment used
for AML is often utilized [71].
B. Haematopoietic stem cell transplantation
Haematopoietic stem cell
transplantation (HSCT) is a well-
established therapeutic option for
patients with myeloid leukemia,
including acute myeloid leukemia
(AML). Allogeneic HSCT, which
involves the transfer of stem cells
from a donor, is particularly effective
in treating AML. However, post-
transplant relapse can occur in a
significant proportion of patients,
leading to a generally poor prognosis
[7]. Relapse rates after allogeneic
HSCT range from 25-30%. Despite the
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risk of relapse, allogeneic HSCT
remains the best option for patients
with relapsed or refractory AML [73].
There are several factors that can
influence the outcome of allogeneic
HSCT in AML patients. One study
found that central nervous system
(CNS) relapse after allogeneic HSCT is
associated with poor prognosis.
Additionally, the presence of TP53
mutations in AML patients, which are
associated with high-risk biological
features, can negatively impact the
outcome of allogeneic HSCT).
However, the use of hypomethylating
agents as maintenance therapy after
allogeneic HSCT has shown promise in
improving outcomes for AML patients
[74]. In order to improve the success
of allogeneic HSCT in AML, there have
been efforts to identify predictive
markers for relapse. Next-generation
DNA sequencing has been used to
characterize gene mutations in AML
patients and determine their impact
on post-transplant relapse.
C. Supportive care
Supportive care plays a crucial role in
the management of myeloid leukemia,
providing patients with
comprehensive care to improve their
quality of life and manage symptoms.
Over the past few decades, several
important treatment and supportive
care strategies have been
implemented to address the complex
needs of patients with acute myeloid
leukemia (AML). Integrated palliative
care has been shown to lead to
improvements in quality of life and
mood for patients with AML during
intensive chemotherapy [75]. Early
palliative/supportive care in AML has
been associated with high frequency
of quality indicators for palliative care
and low rates of treatment
aggressiveness at the end of life. This
approach allows for a more patient-
centered and holistic approach to care,
addressing not only the physical
symptoms but also the psychosocial
and emotional needs of patients [76].
In addition to palliative care, emerging
immunotherapy approaches have
shown promise in the treatment of
AML. Intensive chemotherapy with or
without hematopoietic stem cell
transplantation has been the mainstay
of curative treatment for AML, but for
relapsed/refractory or intolerable
cases, immunotherapy and palliative
care may be necessary.
Immunotherapy, including immune
checkpoint inhibitors and adoptive
immunotherapy, has shown potential
in improving outcomes for patients
with AML. However, it is important to
monitor and manage adverse events
associated with these therapies to
ensure symptomatic treatment and
optimal patient care. Supportive care
is also essential in the management of
myelodysplastic syndromes (MDS), a
group of hematologic disorders that
can progress to AML. Transfusion
support, management of iron
overload, antimicrobial prophylaxis,
routine immunizations, and palliative
care interventions are among the
supportive care interventions used in
patients with MDS. Palliative care in
the MDS population aims to address
the physical, emotional, and
psychosocial needs of patients,
providing symptom management and
improving quality of life [77]. In the
context of pediatric palliative care,
nurses play a crucial role in providing
evidence-based and competence-
based care to children with leukemia.
They are positioned to provide holistic
palliative care, addressing the
physical, emotional, and psychosocial
needs of both the child and their
family. The challenges experienced by
nurses in providing pediatric
palliative care include managing
symptoms, addressing psychosocial
needs, and ensuring continuity of care
[78].
D. Clinical trials and experimental therapies
Clinical trials and experimental
therapies play a crucial role in
advancing the treatment options for
myeloid leukemia. Several studies
have investigated different
approaches to improve outcomes for
patients with acute myeloid leukemia
(AML) and other forms of myeloid
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leukemia. Here, we will discuss some
of the recent research findings and
experimental therapies in the field.
One promising approach is the use of
targeted therapies. For example, a
small molecular Polo-like kinase 1
(PLK1) inhibitor called volasertib has
shown potential in clinical trials for
the treatment of refractory AML.
Volasertib, in combination with
cytarabine, has reached phase III
clinical trials and has demonstrated
efficacy in patients with refractory
AML [79]. This targeted therapy aims
to inhibit PLK1, a protein involved in
cell cycle regulation, to disrupt the
growth of leukemic cells. Another
targeted therapy being investigated is
the use of cereblon E3 ligase
modulating drugs (CELMoDs). One
specific CELMoD, CC-90009, is
currently in clinical trials for the
treatment of AML. These drugs work
by modulating the activity of cereblon,
a protein involved in protein
degradation, to selectively target
leukemic cells. Immunotherapy has
also emerged as a promising approach
for the treatment of myeloid leukemia.
Allogeneic hematopoietic stem cell
transplantation (allo-HSCT) has been a
cornerstone of immunotherapy for
AML and other hematologic
malignancies, offering the potential
for cure in a subset of patients.
Chimeric antigen receptor (CAR) T-cell
therapy is another form of
immunotherapy that has shown
promise in the treatment of AML. CAR-
T cells targeting CD7 have
demonstrated significant antitumor
efficacy against relapsed and
refractory AML in preclinical and
clinical studies [80.
Advances in myeloid leukemia research
A. Genetics and molecular insight
Genetics and molecular insights play a
crucial role in understanding and
advancing research on myeloid
leukemia. Myeloid leukemia is a
malignant disorder characterized by
the uncontrolled proliferation of
malignant myeloid progenitor cells
and various genetic and molecular
abnormalities [81]. The molecular
diversity and evolution of acute
myeloid leukemia (AML) have been
extensively studied, providing
valuable insights into the disease.
Acute promyelocytic leukemia (APL), a
subtype of AML, has a distinctive
molecular pathophysiology and
clinical manifestationsibility and
variability of myeloid neoplasms,
includi. Genetic polymorphisms have
been found to influence the susceptng
AML [82]. Genetic alterations, such as
fusion genes, are commonly observed
in myeloid leukemia. For example, the
coexistence of the BCR-ABL fusion
gene and JAK2V617F mutation has
been reported in resistant chronic
myeloid leukemia. Fusion genes, such
as ETV6-NCOA2, have been shown to
induce T/myeloid mixed-phenotype
leukemia. The identification of these
fusion genes and their role in
leukemogenesis provides valuable
insights into the molecular
mechanisms underlying myeloid
leukemia. Furthermore, the
dysregulation of specific genes and
signaling pathways has been
implicated in the pathogenesis of
myeloid leukemia. For instance, the
co-targeting of c-Myc and Bcl-2 has
been shown to effectively control AML
in preclinical models [83]. Epigenetic
mechanisms also play a critical role in
the development and progression of
myeloid leukemia. Alterations in DNA
methylation and histone
modifications have been implicated in
the dysregulation of gene expression
in AML. The identification of
intrinsically disordered regions in hub
genes of AML has provided insights
into the protein-protein interaction
networks and gene expression profiles
associated with the disease [84].
Advancements in molecular
diagnostics have greatly contributed
to the understanding and management
of myeloid malignancies. Optical
genome mapping has been used to
detect genomic aberrations in AML,
aiding in diagnostic subtyping,
prognosis, and patient management.
The use of RNAi prodrugs has shown
promise in decreasing elevated mRNA
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levels of specific genes in pediatric
AML patients [85].
B. Immunotherapy and CAR-T cell therapy
Immunotherapy and CAR-T cell
therapy have emerged as promising
approaches for the treatment of
myeloid leukemia, including acute
myeloid leukemia (AML) and chronic
myeloid leukemia (CML). These
therapies aim to harness the power of
the immune system to target and
eliminate leukemia cells.One approach
to immunotherapy in myeloid
leukemia is the use of chimeric
antigen receptor (CAR) T cell therapy.
CAR-T cells are engineered to express
a receptor that recognizes specific
antigens on the surface of leukemia
cells, allowing them to selectively
target and kill these cells. For example,
CAR-T cells targeting interleukin-1
receptor accessory protein (IL-1RAP)
have shown promise in targeting
leukemic stem cells in CML and AM
[86]. However, CAR-T therapies
targeting myeloid-lineage antigens
such as CD123 and CD33, which are
commonly expressed on leukemia
cells, may have potential
hematopoietic toxicity [87]. Another
approach to immunotherapy in
myeloid leukemia is the use of natural
killer (NK) cells, T cells, and dendritic
cells. These immune cells play
important roles in immune monitoring
and anti-leukemia responses.
Strategies that utilize these cells, such
as adoptive immunotherapy, have
shown promise in preclinical and
clinical studies. For example, CD38-
directed CAR-T cell therapy has been
explored as a novel immunotherapy
strategy for myeloid chronic myeloid
leukemia (CML) despite the progress in
immunotherapy for myeloid leukemia;
there are still challenges that need to
be addressed. One challenge is the
toxicity of CAR-T cell therapy on
normal hematopoietic cells, which can
limit its efficacy. Strategies to enhance
CAR-T cell persistence and reduce
toxicity are being explored, such as
the use of inducible caspase 9 suicide
gene safety switches [86].
C. Precision medicine approaches
Precision medicine approaches in
myeloid leukemia have gained
significant attention in recent years.
The mutational and epigenetic
landscape of acute myeloid leukemia
(AML) has been extensively studied,
providing valuable insights into
potential biological targets for
precision medicine. Proteomic
characterization of AML has also been
explored, aiming to identify specific
protein markers that can guide
personalized treatment strategies. In
the management of AML, precision
medicine has shown promise in older
adults. For instance, the use of
magrolizumab, an anti-CD47 antibody,
has demonstrated good efficacy in
older or unfit treatment-naïve as well
as relapsed/refractory AML patients
[88]. Furthermore, the role of vitamin
D in the diagnosis of AML has been
investigated. Studies have shown a
significant inverse correlation
between serum cholesterol levels and
AML, suggesting a potential role for
vitamin D in the diagnosis and
management of the disease.
Furthermore, the transformation of
AML to acute B cell lymphoblastic
leukemia has been observed in the
context of CAR-T cell therapy,
highlighting the need for careful
monitoring and management of
treatment-related complications [89].
Overall, precision medicine
approaches in myeloid leukemia hold
great promise for improving patient
outcomes. By understanding the
mutational and epigenetic landscape,
proteomic profiles, and specific
genetic markers, personalized
treatment strategies can be developed
to target the underlying molecular
abnormalities in AML. However,
further research is needed to validate
and optimize these approaches for
clinical implementation.
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Prognosis and survival rates
A. Factors affecting prognosis
Factors affecting prognosis in myeloid
leukemia can be influenced by various
patient-specific and disease-specific
factors. Several studies have
investigated these factors to better
understand their impact on prognosis.
One study by focused on the
relationship between transfusion
amounts, old age, and survival in adult
acute leukemia patients who survived
beyond 100 days. The study found
that transfusion amounts were
associated with old age and survival in
these patients. This suggests that
transfusion amounts may be a factor
that affects prognosis in myeloid
leukemia.Another study by Zhu et al.
[90] investigated the prognostic
factors of acute myeloid leukemia
through retrospective analysis. The
study aimed to identify factors that
could influence the prognosis of
patients with this type of leukemia. By
analyzing various clinical and
laboratory parameters, the study
found that certain factors, such as age,
white blood cell count, and
cytogenetic abnormalities, were
associated with prognosis. These
findings suggest that age, white blood
cell count, and cytogenetic
abnormalities may be important
factors affecting prognosis in myeloid
leukemia.
B. Treatment outcomes
Treatment outcomes in myeloid
leukemia have improved over the
years due to advancements in
therapeutic approaches and targeted
therapies. One promising combination
therapy is the use of Venetoclax and
Azacitidine, which has shown
impressive results in newly diagnosed
elderly patients with acute myeloid
leukemia and refractory/relapsed
disease. This combination has
demonstrated efficacy in improving
treatment outcomes and has the
potential to be a valuable treatment
option. Immunotherapy, particularly
allogeneic hematopoietic stem cell
transplantation (allo-HSCT), has been a
cornerstone in the treatment of acute
myeloid leukemia (AML) and other
hematologic malignancies. Allo-HSCT
offers the potential to cure a subset of
patients and has been widely used for
decades. However, the use of immune
checkpoint inhibitors and chimeric
antigen receptor (CAR) T-cell therapy
has also shown promise in the
treatment of AML. CAR-T therapies
targeting myeloid-lineage antigens
such as CD123 and CD33 have been
developed, although they may have
potential hematopoietic toxicity [87].
These immunotherapeutic approaches
provide alternative treatment options
for patients with AML. Genetic
abnormalities and mutations play a
significant role in the prognosis and
treatment outcomes of myeloid
leukemia. For example, mutations in
the CEBPA gene have been associated
with acute myeloid leukemia and can
impact treatment response and
clinical outcomes [91]. Similarly,
mutations in the FLT3 gene have been
identified as poor prognostic factors
in pediatric acute myeloid leukemia
[92]. Understanding the genetic
landscape of myeloid leukemia can
help guide treatment decisions and
improve patient outcomes. The use of
tyrosine kinase inhibitors (TKIs) has
revolutionized the treatment of
chronic myeloid leukemia (CML). TKIs,
such as Imatinib and Nilotinib, have
significantly improved the prognosis
and survival of patients with CML.
These targeted therapies specifically
inhibit the abnormal signaling
pathways associated with CML,
leading to disease control and
improved outcomes.In recent years;
the use of Venetoclax has gained
attention in the treatment of acute
myeloid leukemia. Venetoclax has
shown efficacy in relapsed/refractory
AML, although there are some
concerns regarding hematological and
non-hematological adverse events
[93]. Further research and clinical
trials are needed to optimize the use
of Venetoclax and improve treatment
outcomes in AML.Additionally, the
management of acute myeloid
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leukemia in specific patient
populations, such as those with Down
syndrome, requires alternative
chemotherapy approaches [94].
Patient experience and quality of life
A. Coping with a myeloid leukemia diagnosis
Coping with a myeloid leukemia
diagnosis can be a challenging and
overwhelming experience for patients.
It is important for patients to have
access to information and support to
help them navigate through this
difficult time. Several studies and
articles provide insights into various
aspects of coping with a myeloid
leukemia diagnosis.One study by
Talwar et al. [95] highlights the
challenges faced by healthcare
systems and clinicians in managing
acute myeloid leukemia (AML)
patients, particularly in the context of
immunocompromised states. This
information can be valuable for
patients diagnosed with CML, as it
provides insights into treatment
options and their effectiveness. In the
case of undiagnosed chronic myeloid
leukemia in patients with pre-existing
poorly controlled diabetes mellitus
(DM), it is crucial to recognize the
condition and provide appropriate
systemic chemotherapy, as
highlighted by Falah et al. (2023). This
study emphasizes the importance of
early diagnosis and tailored treatment
for patients with comorbidities. Flow
cytometry immune phenotyping is a
powerful tool for accurate diagnosis of
acute leukemias, as mentioned in a
study by (Pandey, 2021). This
information can help patients
understand the diagnostic process and
the significance of flow cytometry in
determining the lineage of their
leukemia.For patients with
relapsed/refractory acute myeloid
leukemia, Venetoclax therapy may be
a promising treatment option, as
suggested by [93]. However, it is
important for patients to be aware of
potential adverse events and the need
for close monitoring during
treatment.The heterogeneity of acute
myeloid leukemia (AML) and its
prognostic factors are discussed in a
study by [96]. This information can
help patients understand the
variability of their condition and the
factors that may influence their
prognosis and treatment decisions.
Myeloid sarcoma, a rare manifestation
of acute myeloid leukemia (AML), can
occur at any extramedullary site. This
information can help patients
recognize the potential symptoms and
manifestations of myeloid sarcoma
and seek appropriate medical
attention.Early diagnosis of chronic
myeloid leukemia (CML) is particularly
important, as mentioned in a study by
[97].
B. Supportive care and psychological services
Supportive care and psychological
services are crucial components in the
management of myeloid leukemia,
including acute myeloid leukemia
(AML) and chronic myeloid leukemia
(CML). These services are essential for
addressing the physical and
psychological needs of patients.One
important aspect of supportive care in
myeloid leukemia is the management
of treatment-related complications.
Patients with myeloid leukemia often
experience immunocompromised
states, which make them more
susceptible to infections. For example,
in the case of a young AML patient with
COVID-19 infection, antiviral therapy
and granulocyte colony-stimulating
factor have been successfully used to
manage the infection [95].
Psychological services are also crucial
in the management of myeloid
leukemia. The diagnosis and
treatment of myeloid leukemia can
have a significant impact on the
mental well-being of patients, leading
to anxiety, depression, and other
psychological distress. Therefore,
providing psychological support and
counseling services is important for
helping patients cope with the
emotional challenges associated with
the disease. Hypomethylating agents,
such as azacitidine, have become the
standard of care for patients with
high-risk myelodysplastic syndrome
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or AML who are not eligible for high-
intensity chemotherapy [98]. These
agents have demonstrated efficacy in
improving outcomes for patients with
myeloid leukemia. The role of genetic
factors in myeloid leukemia has also
been investigated. Double RUNX1
mutations, for instance, have been
found to be enriched in acute
leukemias of ambiguous lineage,
which could have implications for
targeted therapies [99].
Future directions and emerging therapies
A. Promising research areas
Promising research areas in myeloid
leukemia encompass various aspects
of the disease, including molecular
therapy, classification, cytochrome
P450 regulation, treatment
approaches, long non-coding RNA,
differentiation therapy, immune
function, novel drug development,
apoptosis induction, antibody-drug
conjugates, PARP inhibitors, tyrosine
kinase inhibitor therapy, therapy-
related neoplasms, chemo-protective
effects, synthetic T-cell biology,
fusion genes, transporter-mediated
drug interactions, prognostic
signatures, ferroptosis-related genes,
obesity in leukemia patients,
combination therapies, ferroptosis,
myeloid sarcoma, cytoplasmic DNA
sensing, and GATA-1S inhibition of
ferroptosis. These research areas
provide valuable insights into the
understanding and treatment of
myeloid leukemia. One promising
research area in myeloid leukemia is
the targeting of mutant FLT3 for
molecular therapy. FLT3 mutations are
well-known targets for therapy in
acute myeloid leukemia (AML). The
role of cytochrome P450 in regulating
the acute myeloid leukemia
microenvironment is another
promising research area. Recent
research has focused on determining
the regulators of cytochrome P450
expression and activity in AML [100].
B.
Potential breakthrough on the horizon
Myeloid leukemia is a complex and
aggressive hematologic malignancy
that requires innovative treatment
approaches. Several recent studies
have explored potential
breakthroughs in the field. One
promising avenue of research is the
use of CAR-T therapy [85]
demonstrated the feasibility of CD7 as
a target for CAR-T therapy in relapsed
and refractory acute myeloid leukemia
(R/R AML). They found that CD7-
directed CAR-T therapy showed
significant antitumor efficacy against
R/R AML. Yan et al. [93] conducted a
systematic review and meta-analysis
of studies evaluating the efficacy and
safety of venetoclax in
relapsed/refractory AML. They found
that venetoclax had a positive impact
on overall survival in these patients.
This highlights the potential of
venetoclax as a therapeutic option for
AML patients who have relapsed or are
refractory to standard treatments.
CONCLUSION
In conclusion, the advancements in
myeloid leukemia treatment have
showcased remarkable progress,
revolutionizing patient care and
outcomes. Over the years, significant
strides have been made in
understanding the complex biology of
myeloid leukemia subtypes, leading to
the development of targeted therapies
and personalized treatment
approaches. The introduction of novel
targeted agents, immunotherapies,
and advancements in bone marrow
transplantation techniques have
substantially improved survival rates
and quality of life for patients.
Additionally, the integration of
precision medicine, molecular
profiling, and minimal residual
disease monitoring has allowed for
more tailored and effective therapies,
minimizing adverse effects and
improving long-term prognosis.
However, despite these remarkable
advancements, challenges persist,
including drug resistance, relapse, and
access to cutting-edge therapies for all
patients. Further research efforts
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focusing on overcoming resistance
mechanisms, identifying new
therapeutic targets, and enhancing
accessibility to innovative treatments
are crucial to continue the momentum
in improving outcomes for individuals
affected by myeloid leukemia. In
essence, the landscape of myeloid
leukemia treatment has undergone a
paradigm shift, offering renewed hope
and prospects for better survival rates
and enhanced quality of life.
Continued collaboration between
researchers, healthcare professionals,
patients, and advocacy groups remain
imperative to further advance the field
and ultimately achieve better
outcomes for all individuals affected
by myeloid leukemia.
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CITE AS: Hauwa Ali Buhari, Salisu, Muhammad and Emmanuel Ifeanyi Obeagu (2023). Advancements in
Myeloid Leukemia Treatment: A Comprehensive Update. IAA Journal of Biological Sciences 11(1):12-32.
https://doi.org/10.59298/IAAJB/2023/2.2.23310
