Application of Molecular Karyotyping in Acute Myeloid Leukemia: A Review

Abstract

Acute myeloid leukemia (AML) is an aggressive disease characterized by the overproduction of immature myeloid cells that accumulate in blood and bone marrow. Integration of genetic findings and clinicopathological information is crucial in establishing the diagnosis, prognosis and determining the therapeutic approach in the management of AML patients. In recent years, the AML classification has evolved from morphology to cytogenetics/molecular genetics-based findings, which is essential in the detection of chromosomal abnormalities and has provided the framework for the diagnosis and riskstratification in AML. Moreover, with advances in molecular karyotyping such as comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays, various limitations of conventional diagnostic approaches have been overcome. Hence, this review focuses on the insights into molecular karyotyping using CGH and SNP arrays which enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. Technical hindrances of these methods (e.g. regions of losses, gains, or "undulating waves") are also discussed in the context of AML. Table 1. WHO classification of AML and related neoplasms (2016) [16].AML with recurrent genetic abnormalities AML with t (8;21)(q22;q22.1);RUNX1-RUNX1T1 AML with inv (16)(p13.1q22) or t (16;16)(p13.1;q22);CBFB-MYH11 APL with PML-RARA AML with t (9;11)(p21.3;q23.3);MLLT3-KMT2A AML with t (6;9)(p23;q34.1);DEK-NUP214 AML with inv (3)(q21.3q26.2) or t (3;3)(q21.3;q26.2); GATA2, COM AML (megakaryoblastic) with t (1;22)(p13.3;q13.3);RBM15-MKL1 Provisional entity: AML with BCR-ABL1 AML with mutated NPM1

Neoteric Algorithm Using Cell Population Data (VCS Parameters) as a Rapid Screening Tool for Haematological Disorders

“…Haematological malignancies are the fourth most frequently diagnosed cancer around the world, with an incidence rate of 9% of all cancers [ 3 ]. For decades, the diagnosis of haematological malignancies has relied on morphologic examinations of the subject’s blood or bone marrow aspirates [ 4 ], and by immunophenotype profiling using flow cytometry techniques [ 5 ]. The advent of molecular genetics and genomic technologies, such as polymerase chain reaction (PCR) and sequencing-based methods, enabled deeper insight into the diagnosis and prognosis of various haematological malignancies [ 6 ].…”