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The Myelodysplastic/myeloproliferative category of myeloid neoplasms includes clinical, laboratory, and morphologic features that overlap between MDS and MPN. In this category are included MDS/MPN with ring sideroblasts with marked thrombocytosis, atypical CML, (BCR-ABL1 negative), and chronic myelomonocytic leukemia. JMML and unclassifiable MDS/MPN. In MDS/MPN the karyotype is often normal or shows abnormalities in common with MDS. Mutations are seen in a high proportion of cases, most common being SRSF2, TET2, and or ASXL1 in more than 80% cases. Co-mutation of SRSF2 and TET2 is highly specific for patients with CMML.

Progression of Chronic Myeloid Leukemia from chronic phase to accelerated phase to blast crisis is often associated with secondary chromosomal aberrations, such as trisomy 8, trisomy 19, duplication of Ph chromosome, isochromosome 17 q, acquisition of t(1;21) or translocations and inversions associated with AML/Myelodysplasia and show complex karyotypes.

Cytogenetic studies have become a critical factor in the workup of hematologic neoplasms. They provide invaluable information for diagnosis, prognosis, and clinical decision-making for the disease.

Molecular diagnostic testing has virtually become a routine part of characterization of hematologic malignancies. In addition to confirming or refining or establishing new diagnoses, it is used extensively to stage patients, to follow them for response to therapy and disease recurrence as well as for predicting prognosis.

CLL is often marked by cytogenetic aberrations (up to 80% of patients may show abnormalities by FISH) which are critical in risk stratification. Among them, deletions of 11q, 13q, 17p, and trisomy 12 play an important role in CLL pathogenesis and evolution determining patient outcomes and therapeutic strategies. FISH analysis has been implemented as the gold standard for diagnosis. It has also been used very effectively in the diagnosis of non-Hodgkin’s Lymphoma employing BCL-2, BCL-6, and MYC gene alterations for classification and defining the subgroups of NHLs for determining therapeutic strategies.

Myeloproliferative neoplasms are characterized by a clonal proliferation of one or more hematopoietic cell lineages, predominantly in the bone marrow but sometimes in the liver and spleen. In contrast to MDS, they show terminal myeloid cell expansion into the peripheral blood. They include CML, chronic neutrophilic leukemia (CML) polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia (CEL), mastocytosis, and unclassifiable MPNs.

The use of Next Generation Sequencing is being increasingly sought to be included in routine clinical use for more differentiated disease classification, risk stratification and therapeutic decisions, particularly in AML, MDS, and MPNs. But unexpected challenges are being faced towards interpretation and implementation of the results obtained.