Hyperdiploidy: the longest known, most prevalent, and most enigmatic form of acute lymphoblastic leukemia in children

Leukemia. 2022 Dec;36(12):2769-2783. doi: 10.1038/s41375-022-01720-z. Epub 2022 Oct 20.


Hyperdiploidy is the largest genetic entity B-cell precursor acute lymphoblastic leukemia in children. The diagnostic hallmark of its two variants that will be discussed in detail herein is a chromosome count between 52 and 67, respectively. The classical HD form consists of heterozygous di-, tri-, and tetrasomies, whereas the nonclassical one (usually viewed as "duplicated hyperhaploid") contains only disomies and tetrasomies. Despite their apparently different clinical behavior, we show that 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 indicate that they are biologically more similar than hitherto appreciated. Even though in-depth analyses of the genomic intricacies of classical HD leukemias are indispensable for the elucidation of the disease process, the ensuing results play at present surprisingly little role in treatment stratification, a fact that can be attributed to the overall good prognoses and low relapse rates of the concerned patients and, consequently, their excellent treatment outcome. Irrespective of this underutilization, however, the detailed genetic characterization of HD leukemias may, especially in planned treatment reduction trials, eventually become important for further treatment stratification, patient management, and the clinical elucidation of outcome data. It should therefore become an integral part of all upcoming treatment studies.

Publication types

  • Review

MeSH terms

  • Aneuploidy
  • Child
  • Humans
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Tetrasomy*
  • Treatment Outcome