Clinical, Hematologic, Biologic and Molecular Characteristics of Patients with Myeloproliferative Neoplasms and a Chronic Myelomonocytic Leukemia-Like Phenotype

Abstract

Patients with a myeloproliferative neoplasm (MPN) sometimes show a chronic myelomonocytic leukemia (CMML)-like phenotype but, according to the 2016 WHO classification, a documented history of an MPN excludes the diagnosis of CMML. Forty-one patients with an MPN (35 polycythemia vera (PV), 5 primary myelofibrosis, 1 essential thrombocythemia) and a CMML-like phenotype (MPN/CMML) were comprehensively characterized regarding clinical, hematologic, biologic and molecular features. The white blood cell counts in MPN/CMML patients were not different from CMML patients and PV patients. The hemoglobin values and platelet counts of these patients were higher than in CMML but lower than in PV, respectively. MPN/CMML patients showed myelomonocytic skewing, a typical in vitro feature of CMML but not of PV. The mutational landscape of MPN/CMML was not different from JAK2-mutated CMML. In two MPN/CMML patients, development of a CMML-like phenotype was associated with a decrease in the JAK2 V617F allelic burden. Finally, the prognosis of MPN/CMML (median overall survival (OS) 27 months) was more similar to CMML (JAK2-mutated, 28 months; JAK2-nonmutated 29 months) than to PV (186 months). In conclusion, we show that patients with MPN and a CMML-like phenotype share more characteristics with CMML than with PV, which may be relevant for their classification and clinical management.

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

“…The percentage of patients who progressed to AML in our study was also along the lines of previous reports [ 11 , 22 , 47 , 49 ]. The risk of AML transformation depends on the transformative aggressiveness of CMML and on the competing risk of dying before transformation, usually from comorbidities or consequences of cytopenia [ 37 ].…”

Myelomonocytic skewing in chronic myelomonocytic leukemia: phenotypic, molecular and biologic features and impact on survival

“…In a seminal paper using mutation‐specific discrimination analysis of single‐cell‐derived colonies in 28 patients with CMML, Itzykson et al could show that the main characteristics of this disease are early clonal dominance, arising at the CD34+/CD34‐stage of hematopoiesis, and granulomonocytic differentiation skewing of multipotent and common myeloid progenitors, 10 but this phenomenon has not been correlated to other features such as phenotype and clinical outcome. Since semisolid in vitro cultures from PBMNCs of normal individuals usually contain a higher concentration of BFU‐E as compared to CFU‐GM, this test may be useful for investigating skewed differentiation toward the myelomonocytic over erythroid commitment in patients 8,9 . Due to the fact that in our center the assessment of hematopoietic colony formation in vitro has been an integral part of the diagnostic work up in patients with suspected myeloid malignancies for many years 12 and these data are part of the ABCMML, 11 we had the possibility to analyze the phenomenon of myelomonocytic skewing in a relatively large cohort of patients with CMML in this retrospective study.…”

“…Recently, we have reported that analysis of myelomonocytic skewing in vitro may be useful to investigate skewed differentiation toward the myelomonocytic over erythroid commitment in patients 8,9 . Since the presence of skewing may be associated with a different phenotype, a different mutational landscape and a different prognosis in patients with myeloid malignancies this in vitro test may help to comprehensively study hematopoiesis in patients with complex disturbances of blood formation.…”

Hybrid or Mixed Myelodysplastic/Myeloproliferative Disorders – Epidemiological Features and Overview

“…diseases CMML associated with mastocytosis, CMML and blastic plasmacytoid dendritic cell neoplasm, CMML associated with eosinophilia (77-79), t-CMML(85), pre CMML syndromes (oligo-monocytic CMML)(86,87), CMML with JAK-2 mutation, CMML with rearranged PDGFRA, PDGFRB, FGFR1, PCM1-JAK2, other MPN (MF, PV.) with monocytosis ("MPN with CMML-like phenotype")(88) …”