Cytogenetic landscape in 1012 newly diagnosed chronic lymphocytic leukemia

Eur J Haematol. 2019 Dec;103(6):607-613. doi: 10.1111/ejh.13329. Epub 2019 Oct 1.

Abstract

Background: Chronic lymphocytic leukemia (CLL) stratification mainly relies on FISH markers according to Döhner's hierarchical model which includes high-risk FISH markers, intermediate FISH, or low-risk FISH. Recently, complex karyotype (CK) has been demonstrated as an independent negative prognostic factor in CLL.

Methods: A series of 1012 untreated CLL patients have been investigated with both FISH and chromosome banding analysis (CBA) on the same pellet obtained from interleukin IL-2-CPG DSP30 oligonucleotide-stimulated cultured cells.

Results: Combining both FISH and CBA has led to refine prognostic categories with identification of 30% of CK in low-risk and intermediate FISH group. This raises the issue of switching them to a high-risk group. While this series confirmed the significant association between CK and high-risk FISH (P = .003), 33% of CK present no ATM or TP53 deletion. Three groups characterized by significant association between FISH markers and CBA have emerged: CK with TP53 loss and monosomy 15; CK with ATM loss and 14q32 translocation; and CK without ATM or TP53 losses but trisomies 12, 18, and 19 or t(14;18)(q32;q21).

Conclusion: We have observed that in addition to FISH analysis, the CBA allows detection of many abnormalities with potential impact on patient follow-up and treatment, mainly CK.

Keywords: FISH markers; chronic lymphocytic leukemia; complex karyotype.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Chromosome Banding
  • Female
  • Gene Deletion*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Translocation, Genetic*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins