Bone marrow fibrosis in chronic myelomonocytic leukemia is associated with increased megakaryopoiesis, splenomegaly and with a shorter median time to disease progression.

Kseniya Petrova-Drus,Sharon Barouk-Fox,April Chiu,Attilio Orazi,Elizabeth Margolskee,Julia Geyer,Ahmet Dogan

doi:10.18632/oncotarget.21870

Kseniya Petrova-Drus, Sharon Barouk-Fox + Show 5 more

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https://doi.org/10.18632/oncotarget.21870

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Abstract

Bone marrow (BM) fibrosis is an adverse prognostic marker in several myeloid neoplasms, particularly in myelodysplastic syndrome (MDS) with fibrosis; however, its significance in chronic myelomonoctyic leukemia (CMML) has not been evaluated. We performed a retrospective analysis to investigate the prognostic and clinicopathological features of CMML with and without BM fibrosis. The study included specimens from a total of 83 untreated CMML patients from 2 large institutions. Patients with any amount of BM fibrosis (MF-1 or higher; MF1+) had significantly shorter progression-free survival (MF1+, 28.3 months vs MF0, not reached; p = 0.001, log rank test), splenomegaly (p = 0.016), and increased BM megakaryocytes (p = 0.04) compared to patients without BM fibrosis (MF-0). No association was observed between fibrosis and peripheral blood parameters, presence of JAK2 V617F mutation, BM blasts, or overall survival. Our study demonstrates the importance of assessing BM fibrosis in CMML. Similar to MDS, the presence of BM fibrosis may identify a distinct subgroup of CMML patients (CMML-F) with a more aggressive clinical course.

Highlights

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping myelodysplastic and myeloproliferative features, characterized by persistent peripheral blood (PB) monocytosis (≥ 1 × 109/L), with monocytes comprising ≥ 10% of the PB leukocytes, and the presence of dysplasia in one or more hematopoietic lineages [1]
Our study demonstrates the importance of assessing Bone marrow (BM) fibrosis in chronic myelomonoctyic leukemia (CMML)
No difference was observed between the MF-0 and MF1+ groups with respect to the white blood cell (WBC)-based CMML subtype

Summary

Introduction

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping myelodysplastic and myeloproliferative features, characterized by persistent peripheral blood (PB) monocytosis (≥ 1 × 109/L), with monocytes comprising ≥ 10% of the PB leukocytes, and the presence of dysplasia in one or more hematopoietic lineages [1]. Since the original recognition of this neoplasm by the French-AmericanBritish (FAB) cooperative effort in 1982 [2], CMML has undergone several revisions and has been recognized by the 2001 [3] and 2008 [1] WHO Classifications as part of the overlap group of myelodysplastic/ myeloproliferative neoplasms (MDS/MPN). The FAB classification utilized degree of leukocytosis to identify two prognostic subgroups [2] namely “proliferative” (WBC count ≥ 13 X 109/L) and “dysplastic” (WBC count < 13 × 109/L) subtypes of CMML. This stratification fell to disuse www.impactjournals.com/oncotarget over the years, based on clinical and recently discovered molecular differences in signaling pathways, the 2016 WHO revision re-recognizes these two subgroups [5]

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