Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms

Abstract

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. Nevertheless, none of them is specific to MDS/MPN and current diagnostic criteria do not include molecular data. Even when such alterations can be helpful for differential diagnosis, they should not be used alone as proof of neoplasia because some of these mutations may also occur in healthy older people. Here, we intend to review the main genetic findings across all MDS/MPN overlap syndromes and discuss their relevance in the management of the patients.

Monocytosis at the time of diagnosis has a negative prognostic impact in myelodysplastic syndromes with less than 5% bone marrow blasts

“…Interestingly, we identified a positive correlation between pb monocytosis and a more favorable karyotype. This is in line with the finding that the majority of patients with classical CMML have a normal karyotype [10].…”

The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms

“…Its impact is the conversion of genetic variations to the homozygous state in essential genes, such as JAK2 and CDKN2A at 9p, FLT3 in 13q, TP53 in 17p, and others, including WT1, CBL, RUNX1, and TET, which are related to the initial process or progression of these diseases [ 43 ]. In the context of MPNs, more specifically in PV, this alteration proved to be a common finding, as in other hematological malignancies [ 35 , 39 , 43 ], and defines the molecular scenario of MPNs [ 49 ], with the JAK2V617F variant being reported as present in most patients with MPN [ 48 , 50 ].…”

Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes

“…Interestingly, the aetiology of the inherited MDS is associated with germline predisposition in genes involved in telomere maintenance, DNA repair, biogenesis of ribosomes and cell proliferation. Further detailed reviews on the genetics and clinical implications of various gene mutations in these disorders have been extensively covered elsewhere [7][8][9][10]. Recent studies have suggested that the addition of molecular data to the prognostic scoring systems can improve its predictive applicability in the clinical settings [6,[11][12][13], that will not only help in the clinical diagnosis but can also be used for the monitoring of disease progression.…”