Hyperdiploidy represents the largest genetic entity of B-cell precursor acute lymphoblastic leukemia in children. A recent study discussed in detail the diagnostic hallmark of its two variants, a chromosome count between 52 and 67, respectively.
The classical HD form includes heterozygous di-, tri-, and tetrasomies, whereas the nonclassical one (usually viewed as "duplicated hyperhaploid") contains only disomies and tetrasomies. Although they show apparently different clinical behavior, these two sub-forms can, in principle, be produced by the same chromosomal maldistribution mechanism. Moreover, their respective array, gene expression, and mutation patterns also point toward their biological similarity.
Even though in-depth analyses of the genomic intricacies of classical HD leukemia are indispensable for elucidating the disease process, the subsequent results have surprisingly little impact on treatment stratification. This can be attributed to the patient's overall good prognoses, low relapse rates, and excellent treatment outcomes. However, despite this underutilization, detailed genetic characterization of HD leukemias may be crucial, particularly in planned treatment reduction trials, to further stratify treatment, manage patients, and analyze clinical outcomes. It should thus become an integral part of all upcoming treatment studies.
Leukemia. 2022 Oct 20. doi: 10.1038/s41375-022-01720-z. Epub ahead of print. PMID: 36266323.
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