HJNO Jan/Feb 2021

HEALTHCARE JOURNAL OF NEW ORLEANS I  JAN / FEB 2021 51 Jitendra Gandhi, MD Medical Oncology-Hematology Terrebonne Medical Center cytogenetics abnormalities and clonal pres- sure can selectively proliferate cell lines. Some driver mutations lead to uncontrolled and relentless proliferation of a clone and ultimately to AML. JAK2 mutation can proliferate an RBC clone resulting in PV, or of megakaryocytes to ET, but could be decades before they end in AML. Mutated genes, commonly associated either as single or multiple defects are SF3B1, RUNX1, TET2, DNMT3A, SRSF2, and ASXL1. Some muta- tions may have a higher risk of converting intoAML. Often two to three mutations are present at diagnosis. The more complex the karyotype, the higher the likelihood for con- version to AML. RNA splicing is also being implicated in pathogenesis and perpetuating the syndrome, whereas DNA methylation and histone modification clonal mutations are drivers for clonal progression. These genes can be diagnosed by “liquid biopsies” (i.e., blood tests) and can be serially followed to map progress of the disease. 5q- Syndrome Often an indolent disease, very responsive to lenalidomide. It often presents with mac- rocytic anemia and mild thrombocytosis. Germline Mutations • DDX41 (Dead-BOX RNA Helicase) – usually manifest in early decades as well. Often, they have a very good outcome with favorable responses in nearly 100% of patients with 5-azaciti- dine and can often last over five years; • RUNX1-related platelet disorders; • Fanconi anemia with marrow aplasia – often lethal and needs a transplant; • Diamond-Blackfan anemia (red cell aplasia) – lethal and needs a transplant; • GATA2 deficiency syndrome – associ- ated with other systemic diseases; • MIRAGE syndrome – myelodyspla- sia, infections, restriction of growth, adrenal aplasia, genital phenotypes and enteropathy. Seen in children and young adults. Myelofibrosis While many patients with MDS can convert to leukemia, a few can “burn out” and scar the entire bone mar- row into Myelofibrosis. This often is catastrophic, though new approach- es have appeared in the last few years. Diagnosis and Risk Stratification • Cytopenia of at least one cell line is essential; • High B12 levels because of elevated B12-carrying protein; • Bone marrow examination may show characteristic dysplasia, blasts or fi- brosis. Iron staining for sideroblasts; • Flow cytometry; • Molecular profiling; • Cytogenetics; • Peripheral smear review; Myelodysplastic Syndrome: severe dysplastic changes with multinucleated RBC precursors.