Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome

Patnaik, Mrinal M.; Wassie, Emnet A.; Padron, Eric; Onida, Francesco; Itzykson, Raphaël; Lasho, Terra L.; Kosmider, Olivier; Finke, Christy; Hanson, Curtis A.; Ketterling, Rhett P.; Komrokji, Rami; Tefferi, Ayalew; Solary, Éric

doi:10.1038/bcj.2014.90

Cited by 50 publications

(49 citation statements)

References 24 publications

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“…63 CMML cases in young adults can develop on a background of germ line mutations in RUNX1, 41 GATA2, 64 ANKRD26, 65 or DDX41. 66 Preferred interactions between mutational events may explain the frequent acquisition of somatic ASXL1 on a GATA2-mutated background.…”

Section: Cmml In Younger Patientsmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that may deserve specific management. Defined by a persistent peripheral blood monocytosis ≥1 × 109/L and monocytes accounting for ≥10% of the white blood cells, this aging-associated disease combines cell proliferation as a consequence of myeloid progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor with myeloid cell dysplasia and ineffective hematopoiesis. The only curative option for CMML remains allogeneic stem cell transplantation. When transplantation is excluded, CMML is stratified into myelodysplastic (white blood cell count <13 × 109/L) and proliferative (white blood cell count ≥13 × 109/L) CMML. In the absence of poor prognostic factors, the management of myelodysplastic CMML is largely inspired from myelodysplastic syndromes, relying on erythropoiesis-stimulating agents to cope with anemia, and careful monitoring and supportive care, whereas the management of proliferative CMML usually relies on cytoreductive agents such as hydroxyurea, although ongoing studies will help delineate the role of hypomethylating agents in this patient population. In the presence of excessive blasts and other poor prognostic factors, hypomethylating agents are the preferred option, even though their impact on leukemic transformation and survival has not been proved. The therapeutic choice is illustrated by 4 clinical situations among the most commonly seen. Although current therapeutic options can improve patient’s quality of life, they barely modify disease evolution. Improved understanding of CMML pathophysiology will hopefully lead to the exploration of novel targets that potentially would be curative.

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Section: Cmml In Younger Patientsmentioning

confidence: 99%

How I treat chronic myelomonocytic leukemia

Solary

Itzykson

2017

Blood

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“…Although TET2 mutations are widely prevalent in CMML, they have not been shown to independently impact either OS or LFS [22]. Similar to MDS, where clonal TET2 mutations in the absence of clonal ASXL1 mutations predict for response to hypomethylating agents (HMA) [25], at least in young CMML patients (age <65 years), there seems to be a similar relationship [26].…”

Section: Molecular Abnormalities In Cmmlmentioning

confidence: 99%

Chronic Myelomonocytic Leukemia: a Genetic and Clinical Update

McCullough

Patnaik

2015

Curr Hematol Malig Rep

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Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder, characterized by peripheral blood monocytosis and overlapping features between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Clonal cytogenetic changes are seen in up to 30 % patients, while approximately 90 % have detectable molecular abnormalities. Most patients are diagnosed in the seventh decade of life. Gene mutations in ten-eleven translocation (TET) oncogene family member 2 (TET2) (60 %), SRSF2 (50 %), ASXL1 (40 %), and RAS (20-30 %) are frequent, with only frame shift and nonsense ASXL1 mutations negatively impacting overall survival. With the lack of formal guidelines, management and response criteria are often extrapolated from MDS and MPN. Contemporary molecularly integrated CMML-specific prognostic models include the Groupe Francais des Myelodysplasies (GFM) model and the Molecular Mayo Model, both incorporating ASXL1 mutational status. Hypomethylating agents and allogeneic stem cell transplant remain the two most commonly used treatment strategies, with suboptimal results. Clinical trials exploiting epigenetic and signal pathway abnormalities, frequent in CMML, offer hope and promise.

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“…CMML arises from the clonal outgrowth of a hematopoietic stem cell resulting in expansion of the granulomonocytic compartment in the bone marrow, younger patients, possibly because of a broader access to disease-modifying treatments such as allogeneic stem cell transplantation [8].…”

Section: Introductionmentioning

confidence: 99%