Rapid conversion of chronic myeloid leukemia to chronic myelomonocytic leukemia in a patient on imatinib therapy

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diag nostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to distinguish between ‘normal’, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology.

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“…In other patients, however, the chronic myeloid leukemia may even mask the CMML at the initial diagnosis. 46…”

Section: Introductionmentioning

confidence: 99%

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

et al. 2019

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“…It is unknown if the CMML in this patient developed from a different clone from CML cells or as a consequence of CML therapy. Secondary myeloid neoplasms were attributed to cytotoxic chemotherapy before the TKI era [9] . Two possible causes of TKI-associated secondary myeloid neoplasm have been proposed: TKI therapy unmasking the separate myeloid abnormalities by inhibiting the CML process and TKI side effects on non-CML cells [12] .…”

Section: Discussionmentioning

confidence: 99%

“…Khorashad et al. reported the case of a CML patient who rapidly converted to fatal CMML after imatinib therapy and found that TET2 and ASXL1 were involved in the disease evolution [9] . Genetic mutations independent of BCR-ABL1 fusion were frequently found in Ph-negative and Ph-positive clones in CML patients [1] .…”

Section: Discussionmentioning

confidence: 99%

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Case report: Co-existing chronic myeloid leukemia and chronic myelomonocytic leukemia–A clinically important but challenging scenario

Song

Moscinski

Zhang

et al. 2023

Leukemia Research Reports

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“…In the meantime, rebalancing the perturbed ecosystem of MPN hematopoiesis may be a more achievable goal, and this may include avoiding interventions that promote the outgrowth of clinically aggressive clones by suppressing targetable but nonlethal clones. 229 Clinical management of myeloid malignancies is likely to become more complex.…”

Section: Perspectivementioning

confidence: 99%

Always Stressed but Never Exhausted: How Stem Cells in Myeloid Neoplasms Avoid Extinction in Inflammatory Conditions

Zhao

Deininger

2023

Blood

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Chronic or recurrent episodes of acute inflammation cause attrition of normal hematopoietic stem cells (HSCs) that can lead to hematopoietic failure, but they drive progression in myeloid malignancies and their precursor clonal hematopoiesis (CH). Mechanistic parallels exist between hematopoiesis in chronic inflammation and the continuously increased proliferation of myeloid malignancies, particularly myeloproliferative neoplasms (MPNs). The ability to enter dormancy, a state of deep quiescence characterized by low oxidative phosphorylation, low glycolysis, reduced protein synthesis, and increased autophagy is central to the preservation of long term HSCs and likely MPN SCs. The metabolic features of dormancy resemble those of diapause, a state of arrested embryonic development triggered by adverse environmental conditions. To outcompete their normal counterparts in the inflammatory MPN environment, MPN SCs co-opt mechanisms used by HSCs to avoid exhaustion, including signal attenuation by negative regulators, insulation from activating cytokine signals, anti-inflammatory signaling, and epigenetic reprogramming. We propose that new therapeutic strategies may be derived from conceptualizing myeloid malignancies as an ecosystem out of balance, where residual normal and malignant hematopoietic cells interact in multiple ways, only few of which have been characterized in detail. Disrupting MPN SC insulation to overcome dormancy, interfering with aberrant cytokines circuits that favor MPN cells and directly boosting residual normal HSCs are potential strategies to tip the balance in favor of normal hematopoiesis. While eradicating the malignant cell clones remains the goal of therapy, this may be a more attainable objective in the short term.

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Rapid conversion of chronic myeloid leukemia to chronic myelomonocytic leukemia in a patient on imatinib therapy

Cited by 5 publications

References 15 publications

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

Case report: Co-existing chronic myeloid leukemia and chronic myelomonocytic leukemia–A clinically important but challenging scenario

Always Stressed but Never Exhausted: How Stem Cells in Myeloid Neoplasms Avoid Extinction in Inflammatory Conditions

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