P098 | GENETIC CHARACTERIZATION OF AN ACUTE MYELOID LEUKEMIA CASE WITH COMPLEX KARYOTYPE USING AN INTEGRATED DIAGNOSTIC APPROACH OF MOLECULAR BIOLOGY AND CYTOGENOMICS.

Acute myeloid leukemia (AML) represents a heterogeneous group of diseases that originate from the neoplastic transformation of hematopoietic stem cells, which acquire chromosomal aberrations and/or point mutations. This leads to clonal proliferation and accumulation of leukemic cells in bone marrow and peripheral tissues. According to the WHO and ELN 2022 guidelines, the diagnosis of AML requires a multidisciplinary approach, integrating morphology, immunophenotyping, cytogenetics, and molecular biology. This case report presents a 70 years-old male patient who arrived at the emergency department with severe pancytopenia. Morphological and immunophenotypic examination of the bone marrow biopsy revealed 50% of immature granulocytic elements positive for CD34, CD117 and CD68 antigens. The diagnostic suspicion was suggestive of AML and prompted clinicians to request cytogenetic and molecular characterization of the bone marrow aspirate. Karyotype analysis revealed unidentified additional material on chromosome 12 and a deletion on chromosome 11 (Figure 1C). On the other hand, molecular analysis by next generation sequencing (NGS) identified mutations in the FLT3, SF3B1, and EZH2 genes, as well as copy number variations (CNVs) of deletion on chromosomes 11 and 7. Curiously, the latter was not detected in karyotype analysis. At this point, an Array CGH+SNP experiment was performed to resolve this discrepancy, revealing the presence of chromosome 7 monosomy, in accordance with NGS data (Figure 1A). A fluorescence in situ hybridization (FISH) test with specific probes for chromosome 7 was subsequently carried out on metaphase and interphase cells, revealing two signals in metaphase and one signal in interphase (Figure 1B). These results confirmed the Array CGH+SNP and NGS outcomes. Probably, the monosomy of chromosome 7 was not observed in the karyotype analysis due to the presence of multiple leukemic clones and because this alteration was present in a subclone with a lower mitotic index compared to the dominant clone. In conclusion, the genetic characterization of AML integrating molecular biology and cytogenetics is essential for accurate prognostic risk assessment. In this context, NGS and array CGH+SNP techniques were decisive, allowing the detection of a complex karyotype and classifying the patient into the adverse prognosis category, according to the ELN 2022 guidelines.