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

Sonja Heibl,Michael Gurbisz,Reinhard Stauder,Klaus Geissler,Eva Jäger,Bettina Gisslinger,Michael Pfeilstöcker,Maike Stegemann,Peter Bettelheim,Sigrid Machherndl-Spandl,Josef Thaler,Heinz Gisslinger,Thomas Nösslinger,Rajko Kusec,Agnes Barna,Peter Valent,Gregor Hoermann,Gökhan Uyanik

doi:10.3390/cancers12071891

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.

Highlights

Among the phenotypic diversity of patients with chronic myelomonocytic leukemia (CMML), peripheral blood (PB) monocytosis is a common prerequisite diagnostic criterion
The age of patients with myeloproliferative neoplasm (MPN)/CMML was higher than that of MPN
There was a male predominance in MPN patients with a CMML phenotype, which was not different from either MPN

Summary

Introduction

Among the phenotypic diversity of patients with chronic myelomonocytic leukemia (CMML), peripheral blood (PB) monocytosis is a common prerequisite diagnostic criterion. In the 2016 WHO classification, persistent PB monocytosis ≥ 1 × 109 /L with monocytes accounting for ≥10% of the leukocytes is required to meet the criteria of CMML. In patients with polycythemia vera (PV), monocytosis has been shown to be associated with a more unfavorable outcome [1]. Monocytosis is a powerful and independent predictor of inferior survival in primary myelofibrosis (PMF) [2,3]. These findings indicate that there is a significant overlap between CMML and MPN, which is supported by the fact that CMML has been placed into the MPN/MDS category since 2000 [4]

Methods

Results

Conclusion