MDS overlap disorders and diagnostic boundaries

Abstract

Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). These disorders are characterized by hematopoietic dysplasia with increased proliferation of monocytes, neutrophils, or platelets. They may have mutational profiles that distinguish them from the disorders they resemble and reflect important differences in pathophysiology. MDS also shares diagnostic borders with other diseases. For example, aplastic anemia and hypoplastic MDS can be difficult to distinguish in patients with pancytopenia and bone marrow hypocellularity. Genetic features may help in this regard, because they can identify differences in prognosis and risk of progression. The boundary between MDS and secondary acute myeloid leukemia (sAML) is arbitrarily defined and has been redefined over the years. Genetic studies have demonstrated that sAML clones can precede clinical progression from MDS by many months, suggesting that MDS with excess blasts could be viewed as an overlap between a dysplastic bone marrow failure syndrome and an oligoblastic leukemia. This review will describe the diagnostic boundaries between MDS, MDS/MPNs, sAML, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, and aplastic anemia and how genetic approaches may help to better define them.

Not Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome Studies

“…Myelodysplastic syndromes (MDS) are a group of clonal heterogenous hematologic malignancies frequent in the elderly, characterized by progenitor cell dysplasia, ineffective hematopoiesis and a high rate of transformation to AML [90]. Due to the not clearly defined boundaries between MDS and other myeloid disorders, establishing MDS diagnosis with conventional method is often problematic.…”

<p>Ruxolitinib Plus Decitabine Effectively Treats Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, by Decreasing the Variant Allele Frequency of <em>KRAS</em></p>

“…5 This disorder is more likely to harbour gene mutations in epigenetic regulators or splicing factors that are related to morphologic dysplasia in conjunction with mutations associated with the activation of growth factor signalling pathways. 5 Meggendorfer M demonstrated that MDS/MPN-U tended to be associated with mutations in epigenetic regulation, the JAK-STAT pathway and splicing but marginally carried RAS pathway-associated mutations. 6 In addition, RAS pathway mutations often coexist with RUNX1, GATA2, and STAG2 mutations.…”

Prognostic Markers of Myelodysplastic Syndromes

“…It is equally important to assess quantitative and qualitative changes. Diagnosing MDS is challenging; for example, at early stages, it is quite difficult to differentiate minor morphological changes associated with dysplasia from other BM deficiencies [ 7 ]. As any MDS diagnosis relies on morphological evidence, opinions may be inconsistent [ 8 ].…”