Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia

Abstract

According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms has made it clear that there are some specific genetic abnormalities in these 3 rare diseases. At the same time, there is considerable overlap among these disorders at the molecular level. The various combinations of genetic abnormalities indicate a multi-step pathogenesis, which likely contributes to the marked clinical heterogeneity of these disorders. This review focuses on the current knowledge and challenges related to the molecular pathogenesis of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia and relationships between molecular findings, clinical features and prognosis.

Figure 1

Somatic mutations affect genes involved in CSF3R (A), epigenetic regulation (B) and RNA splicing (C).

Figure 2

A schematic approach, outlining the evaluation for a patient presenting with peripheral blood leukocytosis. * Molecular genetics test should include mutations involved JAK2, CALR, MPL, CSF3R, TET2, SRSF2, ZRSR2, ASXL1, SETBP1 and BCR-ABL1 fusion genes and rearrangement of PDGFRA, PDGFRB or FGFR1. AML, Acute myeloid leukaemia; CML, chronic myelogenous leukemia; CNL,Chronic neutrophilic leukemia; CMML, chronic myelomonocytic leukemia; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; MDS/MPN, myelodysplastic/myeloproliferative neoplasms.