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Bone marrow biopsy and aspiration at diagnosis. (A) Bone marrow biopsy shows increased cellularity up to 90% (H&E, ×100). (B) Bone marrow aspiration shows myeloid hyperplasia with increased eosinophils (Wright-Giemsa staining, ×1,000). (C) Bone marrow aspiration shows increased mature forms of plasma cells (WrightGiemsa staining, ×1,000).
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Background
Data on Chronic Myeloid Leukemia (CML) prevalence are scarce. Here we provide an estimation of the prevalence of CML in France for the year 2014 using French national health insurance data.
Methods
We selected patients claiming reimbursement for tyrosine kinase inhibitors (TKI) or with hospital discharge diagnoses for CML, BCR/ABL‐posit...
Chronic myeloid leukemia (CML) is a hematological disease, and imatinib (IM) resistance represents a major problem for its clinical treatment. In the present study, the role of tribbles pseudokinase 2 (TRIB2) in IM resistance of CML and the possible mechanism were investigated. It was found that TRIB2 was highly expressed in IM‑resistant patients w...
Citations
... Moreover, murine DN2 with a known human NUP98-HOXD13 (NHD13) fusion transcript have a predisposition to transform into a highly aggressive AML with similar gene expression profiles of several human AML subsets, including those with NPM1 mutations, MLL fusions and NUP98 fusions (103,104). While rare, several case reports have described AML with involvement of the thymus/ mediastinum without evidence of BM infiltration (105)(106)(107)(108). Together, these studies pose the possibility that the thymus can be involved in the leukemogenesis of AML, and some subsets of AML might originate from thymic precursors. ...
Understanding the factors which shape T-lymphocyte immunity is critical for the development and application of future immunotherapeutic strategies in treating hematological malignancies. The thymus, a specialized central lymphoid organ, plays important roles in generating a diverse T lymphocyte repertoire during the infantile and juvenile stages of humans. However, age-associated thymic involution and diseases or treatment associated injury result in a decline in its continuous role in the maintenance of T cell-mediated anti-tumor/virus immunity. Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that mainly affects older adults, and the disease’s progression is known to consist of an impaired immune surveillance including a reduction in naïve T cell output, a restriction in T cell receptor repertoire, and an increase in frequencies of regulatory T cells. As one of the most successful immunotherapies thus far developed for malignancy, T-cell-based adoptive cell therapies could be essential for the development of a durable effective treatment to eliminate residue leukemic cells (blasts) and prevent AML relapse. Thus, a detailed cellular and molecular landscape of how the adult thymus functions within the context of the AML microenvironment will provide new insights into both the immune-related pathogenesis and the regeneration of a functional immune system against leukemia in AML patients. Herein, we review the available evidence supporting the potential correlation between thymic dysfunction and T-lymphocyte impairment with the ontogeny of AML (II-VI). We then discuss how the thymus could impact current and future therapeutic approaches in AML (VII). Finally, we review various strategies to rejuvenate thymic function to improve the precision and efficacy of cancer immunotherapy (VIII).
... Synchronous cases of plasma cell myeloma and other hematologic malignancy are very rare. Reported cases in the literature include plasma cell myeloma and acute myeloid leukemia [7][8][9], plasma cell myeloma and non-Hodgkin (T-cell) lymphoma [10][11][12], and plasma cell myeloma and a myeloproliferative neoplasm [13,14]. Only sporadic reports of B-ALL developing after treatment of plasma cell myeloma or plasma cell myeloma arising after therapy for B-ALL have been described in the literature [1][2][3][4][5][6]. ...
A synchronous diagnosis of a plasma cell neoplasm (PCN) and a non-plasma cell hematologic malignancy is very rare. We report what we believe is the first instance of a synchronous PCN and B lymphoblastic leukemia/lymphoma (B-ALL) diagnosed at initial presentation. The patient underwent laboratory evaluation for an underlying plasma cell neoplasm, including immunology studies, bone marrow biopsy, and flow cytometry immunophenotyping. Serum lambda free light chain and serum IgG were elevated, with an IgG lambda M-protein identified by serum protein electrophoresis and immunofixation. The clinical working diagnosis was plasma cell myeloma. Bone marrow biopsy was positive for a composite PCN and B-ALL. The patient received treatment with VDT-PACE chemotherapy followed by autologous stem cell transplant and maintenance therapy with bortezomib/daratumumab and is in complete remission for both diseases 3.5 years after diagnosis. This case not only adds to the known repertoire of hematologic neoplasms that can occur in association to a PCN, but also demonstrates that patients presenting with this rare combination of hematopoietic neoplasms can be effectively treated simultaneously with excellent responses. Additional research is warranted to understand the pathophysiology, to identify potential prognostic factors, and to develop specific therapeutic plans for these patients.
... трансформации различных гемопоэтических клеточных линий и не имеют общую клетку-предшественницу [4]. Генез возникновения ММ и ХМЛ у одного человека в настоящее время остается до конца неясным, однако существует несколько гипотез, пытающихся объяснить данный феномен [5][6][7][8][9]. ...
Intoduction . Multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are two haematological malignancies developing through tumour transformation of lymphoid and myeloid progenitor cells, respectively, not sharing a common ancestry. Coexistence of the two diseases is extremely rare.
Aim . Clinical description of a patient diagnosed with CML in a few months after start of MM therapy.
Main findings . We report a clinical case of MM and CML in a 62 years-old female patient. MM was diagnosed newly and followed by 5 VD chemotherapy cycles. Treatment discontinued due to severe polyneuropathy. The patient was transferred to thalidomide maintenance therapy. CML was diagnosed 12 months after initiation of thalidomide therapy: BCR-ABL (p190), BCR-ABL (p210). Since imatinib produced short-term effect, dasatinib therapy was started. Following 16 months after the onset of dasatinib therapy, MM relapse and CML progression were diagnosed.
... Although rare, there are numerous case reports of AML involving the thymus or mediastinum without evidence of BM involvement, suggesting that the leukemia may have been initiated in the thymus of these patients [37][38][39][40] . These leukemias have been referred to as myeloid sarcoma or mediastinal granulocytic sarcoma. ...
Transgenic mice that express either a NUP98–PHF23 (NP23) or NUP98-HOXD13 (NHD13) fusion in the hematopoietic compartment develop a wide spectrum of leukemias, including myeloid, erythroid, megakaryocytic and lymphoid, at age 9–14 months. NP23-NHD13 double transgenic mice were generated by interbreeding NP23 and NHD13 mice. Remarkably, 100% of the NP23-NHD13 double transgenic mice developed acute myeloid leukemia (AML) within three months, characterized by replacement of the thymus with leukemic myeloblasts. The marked infiltration of thymus led to the intriguing hypothesis that AML generated in NP23-NHD13 mice arose in the thymus, as opposed to the bone marrow (BM). Transplantation of CD4-CD8- double negative (DN) thymocytes (which were also negative for Mac1 and Gr1) from leukemic NHD13/NP23 mice demonstrated that DN thymocytes could transmit AML, and limiting dilution studies showed that leukemia initiating cells were increased 14-fold in the thymus compared to BM. Further thymocyte fractionation demonstrated that DN1 and DN2, but not DN3 or DN4 fractions transmitted AML, and a marked expansion (100-fold) of Lineage-Sca1 + Kit + (LSK) cells in the thymus of the NP23-NHD13 mice. Taken together, these results show that the thymus of NP23-NHD13 mice acts as a reservoir for AML initiating cells and that thymic progenitors can transmit AML.
... 4 200 patients were reviewed in a study who were treated for chronic granulocytic leukemia and in that study 6 patients had a secondary synchronous or metachronous neoplasm and none was the squamous cell carcinoma of the cervix (Gola et al). 5 Synchronous malignancy of carcinoma penis and CML has been reported (Ganapule et al., 2014). 6 Case report of CML with multiple myeloma (Lee et al., 2017) 7 and breast carcinoma (A Bahl et al., 2010) 8 has also been published. Synchronous CML and cervical malignancy has been found in our patient. ...
... 4 200 patients were reviewed in a study who were treated for chronic granulocytic leukemia and in that study 6 patients had a secondary synchronous or metachronous neoplasm and none was the squamous cell carcinoma of the cervix (Gola et al). 5 Synchronous malignancy of carcinoma penis and CML has been reported (Ganapule et al., 2014). 6 Case report of CML with multiple myeloma (Lee et al., 2017) 7 and breast carcinoma (A Bahl et al., 2010) 8 has also been published. Synchronous CML and cervical malignancy has been found in our patient. ...
... Although rare, there are numerous case reports of AML involving the thymus or mediastinum without evidence of BM involvement, suggesting that the leukemia may have been initiated in the thymus of these patients [37][38][39][40] . These leukemias have been referred to as myeloid sarcoma or mediastinal granulocytic sarcoma. ...
