Myelofibrosis-type megakaryocyte dysplasia (MTMD) as a distinct category of BCR::ABL-negative myeloproliferative neoplasms. Challenges and perspectives

Abstract

In this Perspective, we discuss criteria for defining a new disease entity or variant of a recognized disease or disorder. We do so in the context of the current topography of the BCR::ABL-negative myeloproliferative neoplasms (MPNs) where two new variants are reported: clonal megakaryocyte dysplasia with normal blood values (CMD-NBV) and clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). The cardinal feature of these variants is bone marrow megakaryocyte hyperplasia and atypia corresponding the WHO histological criteria for primary myelofibrosis (myelofibrosis-type megakaryocyte dysplasia-MTMD). Persons with these new variants have a different disease course and features from others in the MPN domain. In a broader context we suggest myelofibrosis-type megakaryocyte dysplasia defines a spectrum of related MPN variants including CMD-NBV, CMD-IT, pre-fibrotic myelofibrosis and overt myelofibrosis, which differ from polycythemia vera and essential thrombocythemia. Our proposal needs external validation and we stress the need for a consensus definition of the megakaryocyte dysplasia which is the hallmark of these disorders.

Concerns regarding myelofibrosis-type megakaryocyte dysplasia

“…Based on the aforementioned characteristics of atypical megakaryocytes, Barosi et al [ 3 ] recently introduced the term of myelofibrosis-type megakaryocyte dysplasia (MTMD) to encompass a group of related MPN variants: persons with clonal megakaryocyte dysplasia with normal blood values (CMD-NBV), persons with clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT) and persons with pre-PMF or overt-PMF. The definition of MTMD originated from megakaryocyte morphology and provided a novel perspective for understanding the clinicopathology of MPNs.…”

“…Firstly, persons with CMD-NBV were typically diagnosed in the context of recent or past vein thrombotic event in atypical site or unexplained arterial thrombosis with or without driver mutations [ 3 ]. However, a question arises regarding how to approach bone marrow biopsy in persons who do not exhibit abnormal blood values nor suffer thrombosis or driver mutations.…”

“…This includes determining whether they maintain a steady state over a long period or follow an evolutionary pattern step by step or by leaps and bounds. Thirdly, it is megakaryocyte morphology that has been emphasized by MTMD on histological grounds [ 3 ]. The development from PV and ET toward post-PV MF and post-ET MF represents a biological continuum with synchronous occurrence of megakaryocyte hyperplasia and atypia, resembling the histomorphologic features of MTMD [ 2 ].…”

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis‐type megakaryocyte dysplasia

“…Recently, two new cognate phenotypes, that is, clonal megakaryocyte dysplasia with normal blood values (CMD‐NBV), and clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD‐IT) have been proposed [1, 2]. These entities, along with prefibrotic myelofibrosis (pre‐MF) and overt‐MF were unified by bone marrow (BM) myelofibrosis‐type megakaryocyte dysplasia (MTMD) [3].…”

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

“…Myeloproliferative neoplasms (MPN) are clonal disorders of the hematopoietic stem cell characterized by a significant increase in one or more lineages of myeloid cells [ 1 ]. Classical BCR/ABL-negative MPN are a heterogeneous group of hematologic malignancies, including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) [ 2 ]. In these disorders, thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality [ 3 ].…”