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Acute Myeloid Leukemia With Complex Karyotype

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P860-861

2026-09-06

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 Any karyotype with at least three chromosomal aberrations, regardless of their type and the individual chromosomes involved, is designated as “complex” in the absence of the WHO-designated recurrent genetic abnormalities. Several studies have shown that patients with t(8;21), t(16;16)/inv(16) and t(15;17) constitute a separate biologic and clinical entity even if they contain additional abnormalities, because these additional cytogenetic abnormalities do not adversely affect the clinical outcome. Therefore the category of AML patients with a com plex karyotype exclude patients with t(8;21),inv(16)/t(16;16) and t (15;17). Approximately, 10% to 12% of AML patients have three or more chromosome abnormalities whereas 8% to 9% have five or more abnormalities. The incidence of a complex karyotype increases with age. In patients with AML, age 18 to 60, 6% to 8% have three or more chromosomal abnormalities whereas 17% to 19% of patients older than 60 have a complex karyotype. In three large series of AML patients with a complex karyotype analyzed using multicolor FISH, more than 90% of patients had at least five abnormalities, with a median number of chromosomal aberrations being between 6 and 10. Approximately 80% of all patients with a complex karyotype have deletion 5q, followed by deletions 17p and 7q, occurring in approximately 50% of cases. At least 85% of all patients with AML with a complex karyotype showed one of these three deletions. The prognosis of patients with a complex karyotype is generally very poor. Among patients with AML above the age of 60, which constitute the major ity of patients with complex karyotype, only 10% to 44% of those who harbor three or more chromosomal abnormalities achieve a CR, which usually is of very short duration (median 6 to 8 months). CR rates of karyotypically complex patients are slightly higher in younger patients. The number of chromosomal abnormalities is central to the definition of a complex karyotype. Adult patients with hyperdiploidy with 49 to 65 chromosomes is a rare abnormality in AML, less than 2%, and by definition is included in a subgroup of patients with com plex karyotypes, irrespective of the structural abnormalities involved. Patients with only numerical gains should be classified as belonging to the intermediate risk group of patients with AML.

Complex karyotype AML occurs in a heterogeneous group of patients that almost never is associated with mutations in NPM1 nor with biallelic CEBPA genes and infrequently with mutations in FLT3, IDH1/IDH2, DNMT3A, and TET2. In sharp contrast, this subgroup of AML patients are characterized by chromosomal aneuploidy, by structural rearrangements and ∼70% demonstrate point mutations in TP53 gene. Most of the patients with TP53 deletions are accompanied by TP53 mutations in the remaining allele leading to the complete loss of the TP53 activity. Heterozygous TP53 mutations are also common.