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تسجيل

Acute Lymphoblastic Leukemia: Complex and Monosomal 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 , P869-870

2026-09-09

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Complex karyotype (≥3 or ≥5 chromosomal abnormalities) as well as patients with neartriploidy defined as 60 to 78 chromosomes and high hyperdiploidy, as well as the presence of 51 to 65 chromosomes are adverse prognostic factors in adults with ALL independent of MRD status. In a more recent study 9.2% of adult patients with ALL had a complex karyotype and 12.8% had a MK and neither was associated with a worse prognosis when treated with risk-adapted or subtype-oriented protocols. MK did not have an impact on prognosis in Ph-positive ALL irrespective of imatinib treatment.

The lymphoid leukemias associated with Down syndrome (DS-ALL) are almost exclusively B-precursor ALLs. In a recent large series of DS-ALLs, there were only five cases of T-ALL among 700 patients. Also, in a sharp contrast to the myeloid neoplasms, they almost never occur in infants. Clinically the outcome of DS-ALL is significantly worse than sporadic childhood B-cell precursor ALLs because of intrinsic resistance to therapy and increased treatment related mortality. Although all known cytogenetic subgroups of child hood B-cell ALLs have been observed, the common abnormalities such as ETV6/RUNX1 fusion and hyperdiploidy are less frequent.

Up to 60% of DS-ALLs have aberrant expression of the cytokine receptor CRLF2 that is often associated with additional mutations activating JAK-STAT signaling. The aberrant expression of this receptor is caused by genomic rearrangements consisting either of a translocation into the IgH locus control region or a microdeletion upstream to the CRLF2 gene, located on the pseudoautosomal component of the sex chromosomes. This deletion fuses CRLF2 with the promoter of an upstream constitutively expressed P2RY8 gene. Analysis of the breakpoint sequences suggest that this rearrangement is mediated by RAG1 or RAG2 in early B-cell precursors.

Application of high-resolution RNA sequencing, FISH, and CGH+SNP array to 117 consecutive pediatric patients with B-ALL demonstrated that all genetic changes necessary for risk stratification were reliably identified. Specifically, array CGH+SNP proved to be more sensitive in detecting cryptic hyperdiploidy. Hyperdiploid leukemic cells frequently fail to proliferate in culture resulting in an absence of aneuploidy. Moreover, copy-number analysis appears to be a crucial and central diagnostic tool and should be included into a standard workflow for B-ALL patients enrolled in the clinical trials.