Monocytosis in polycythemia vera: Clinical and molecular correlates

Abstract

Monocytosis (absolute monocyte count, AMC ≥ 1 × 10 /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 × 10 /L and 18 (7%) an AMC of ≥1.5 × 10 /L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs. 50% at AMC ≥1 × 10 /L) and TET2/SRSF2 mutations (57%/29% vs. 19%/1% at AMC ≥ 1.5 × 10 /L). In univariate analysis, AMC ≥1.5 × 10 /L adversely affected overall (OS; P = .004; HR 2.6, 95% CI 1.4-4.8) and myelofibrosis-free (MFFS; P = .02; HR 4.4, 95% CI 1.3-15.1) survival; during multivariable analysis, significance was borderline sustained for OS (P = .05) and MFFS (P = .06). Other independent risk factors for OS included unfavorable karyotype (P = .02, HR 3.39, 95% CI 1.17-9.79), older age (P < .0001, HR 3.34 95% CI 1.97-5.65), and leukocytosis ≥15 × 10 /L (P = .004, HR 2.04, 95% CI 1.26-3.29). In conclusion, in the current study, we encountered a higher than expected prevalence of monocytosis in patients with PV and the mutation profile and age distribution of PV patients with monocytosis is akin to those of patients with CMML and might partly contribute to their worse prognosis.

Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure?

“…It was concluded that the TET2 -mutations might be a disease accelerator and disease initiator and sustainer in combination with JAK2 V617F in MPNs [149]. Third, TET2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation [150], which might be explained by enhanced and sustained inflammation in the stem cell compartment [151] Fourth, TET2 deficiency elicits monocytosis in mice and both the TET2 mutation and monocytosis associate with inferior prognosis in MPNs [152–154]. Indeed, this association may explain the high cardiovascular morbidity and mortality in MPN patients with monocytosis and perhaps also the increased mortality associated with secondary cancers [105–108, 120–124, 131].…”

How I investigate chronic myelomonocytic leukemia

“…The presence or development of monocytosis in classical MPN is, indeed, a recognized phenomenon. This has been described mostly in PMF, but can also occur in PV . In the context of a well‐established MPN, subsequent development of monocytosis is considered evidence of disease progression roughly comparable to an “accelerated phase,” and as such associated with a poor prognosis …”

Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis

“…1, 2 Monocytosis, however, is not pathognomic for CMML and can be associated with reactive and clonal processes, including MPN such as polycythemia Vera (PV) and primary myelofibrosis (PMF). 3, 4, 5 On the basis of the flow cytometric expression of CD14/CD16, monocytes can be classified into; classical MO1 (CD14 + /CD16 – ), intermediate MO2 (CD14 + /CD16 + ) and non-classical MO3 (CD14 − /CD16 + ) fractions, with MO1 constituting the major monocyte population (85%) in healthy conditions. 6 A recent publication using multiparametric flow cytometry demonstrated a characteristic increase in classical monocytes (cut off value 94%) in CMML patients, distinguishing them from other causes of reactive and clonal monocytosis.…”

“…4, 5 This has important diagnostic, prognostic and therapeutic implications for affected patients. Our study successfully demonstrates the use of monocyte partitioning by multiparametric flow cytometry to distinguish CMML from MPN with monocytosis.…”