Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) represents a different variant of AML, characterized by its clinical heterogeneity and some genetic peculiarities. The diagnosis is made by the presence of ≥20% blasts combined with ≥50% dysplastic cells in two myeloid lineages; a history of MDS or MDS/myeloproliferative neoplasm; or WHO- and ICC-specified cytogenetic abnormalities. AML-MRC accounts for approximately 25% of adult AML cases, largely in the elderly, who usually present with cytopenias and ineffective hematopoiesis. Cytogenetic abnormalities central to AML-MRC include complex karyotypes (≥3 aberrations), deletions, and monosomies involving chromosomes 5q, 7q, 11q, 12p, 13q, 17p, and isochromosome 17q. Mutations in genes such as ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2 support diagnosis even in the absence of morphologic dysplasia. Cytogenetic techniques, such as chromosomal karyotyping and FISH, are the means by which these changes can be identified for categorization, prognosis, and planning of therapy. Risk stratification categorizes patients into favorable, intermediate, and adverse categories based on cytogenetic and molecular markers. Normal karyotypes and abnormalities not related to MDS are favorable risk features, whereas complex and monosomal karyotypes, high-risk lesions such as monosomy 7, del(5q), del(17p), and TP53 mutations associated with poor survival and resistance to treatment are adverse risk features. For personalized treatment, European LeukemiaNet combines cytogenetics with molecular changes such as NPM1, FLT3, and CEBPA. Recent advances in next-generation sequencing detect subclonal and cryptic mutations that enhance the accuracy of prediction. The presence of one monosomy with structural abnormalities or two or more autosomal monosomies is termed a monosomal karyotype. Monosomy 7 is considered an adverse prognostic factor. Aberrations mechanistically arise from spindle assembly checkpoint defects, centromere/kinetochore dysfunction, mitotic apparatus abnormalities, and DNA damage induced by chemotherapy or radiation. In summary, AML-MRC diagnosis, prognosis, and treatment depend on cytogenetic and molecular testing in an integrated manner which is essential for optimising outcomes in this poor-risk patient population.

Keywords: Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC), Complex Karyotype (CK), Monosomal Karyotype (MK), Minimal Residual Disease (MRD).