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

The WHO-category Myelodysplastic/Myeloproliferative neoplasms (MDS/MPNs) recognizes a unique group of clonal myeloid malignancies exhibiting overlapping features of myelodysplastic as well as myeloproliferative neoplasms. The group consists of chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML), juvenile myelomonocytic leukemia (JMML), myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). The most frequent entity in this category is CMML, while all other diseases are extremely rare. Thus, only very limited data on the epidemiology of these subgroups exists. An appropriate diagnosis and classification can be challenging since the diagnosis is still largely based on morphologic criteria and myelodysplastic as well as myeloproliferative features can be found in various occurrences. The diseases in this category share several features that are common in this specific WHO-category, but also exhibit specific traits for each disease. This review summarizes published data on epidemiological features and offers a brief overview of the main diagnostic criteria and clinical characteristics of the five MDS/MPN subgroups.

Molecular Pathogenesis of BCR-ABL-Negative Atypical Chronic Myeloid Leukemia

Atypical chronic myeloid leukemia is a rare disease whose pathogenesis has long been debated. It currently belongs to the group of myelodysplastic/myeloproliferative disorders. In this review, an overview on the current knowledge about diagnosis, prognosis, and genetics is presented, with a major focus on the recent molecular findings. We describe here the molecular pathogenesis of the disease, focusing on the mechanisms of action of the main mutations as well as on gene expression profiling. We also present the treatment options focusing on emerging targeted therapies.

Atypical Chronic Myeloid Leukemia: New Developments from Molecular Diagnosis to Treatment

Atypical Chronic Myeloid Leukemia, BCR-ABL1 negative (aCML) is a rare hematological entity, included in the group of myelodysplastic (MDS)/myeloproliferative (MPN) overlap syndromes. It is characterized by an aggressive course, a high rate of acute myeloid leukemia (AML) transformation, and a dismal outcome. The clinical presentation includes splenomegaly and leukocytosis with neutrophilia and left-shifted granulocytosis accompanied by granulocytic dysplasia and sometimes multilineage dysplasia. In past years, the disease incidence was likely underestimated, as diagnosis was only based on morphological features. Recently, the improving knowledge in the molecular biology of MDS/MPN neoplasms has made it possible to distinguish aCML from other overlapping syndromes, basing on next generation sequencing. Among the most commonly mutated genes, several involve the Jak-STAT, MAPK, and ROCK signaling pathways, which could be actionable with targeted therapies that are already used in clinical practice, opening the way to tailored treatment in aCML. However, currently, there are few data available for small samples, and allogeneic transplant remains the only curative option for eligible patients.