Near-triploidy and near-tetraploidy in hematological malignancies and mutation of the p53 gene

Abstract

Hyperdiploidy of > or =58 chromosomes is reported in 0.5-3% of hematological malignancies, but reports of near-triploidy (58-80 chromosomes) and near-tetraploidy (81-103 chromosomes), are few. We examined these chromosome abnormalities and analyzed the relationship with the mutation of the p53 gene. Thirty-one of 979 adult patients (3.2%) with hematological malignancies were identified as having near-triploid or near-tetraploid (tri-/tetraploid) chromosomes. These included 11 with B-cell neoplasms, seven with Hodgkin's lymphoma, five with T-cell neoplasms, four with myelodysplastic syndromes and four with acute myeloid leukemias. All patients had concurrent complex chromosome aberrations. Deletion of one allele of the p53 gene was found in two patients and a point mutation of the p53 gene was detected in five patients. Although abnormalities of the p53 gene have been reported in about 10% of hematological malignancies, these were found in seven of 31 (23%) patients with tri-/tetraploidy. These findings suggest that the abnormality of the p53 gene may be closely related with tri-/tetraploidy. The four myelodysplastic syndrome (MDS) patients with tri-/tetraploidy had a significantly worse prognosis than those with diploid cytogenetics (n = 35; P < 0.002). In B-cell neoplasms (n = 3), triploidy was associated with a worse prognosis than tetraploidy (n = 8) and diploidy (n = 130; P < 0.02).

Mutations in a gene encoding a midbody protein in binucleated Reed-Sternberg cells of Hodgkin lymphoma

“…Not surprisingly, some of the most conspicuous mutations in cHL are chromosomal aberrations, and chromosomal instability is strongly implicated in Reed-Sternberg cell formation and cHL pathogenesis. Case series show strong evidence of chromosomal instability and chromosomal aberrations in most cases of HD 27, 28 ; there is a particularly heavy frequency of tetraploidy or near-tetraploidy 29, 30 . It has been speculated that Reed-Sternberg cells or their immediate precursors are derived from a karyotypically aberrant lineage 1 .…”

Single institute study of FLT3 mutation in acute myeloid leukemia with near tetraploidy in Serbia

“…E-mail: vdvd@mailcity.com. (Abe et al 1985;Stirewalt et al 2001;Watanabe et al 2004). The investigation of the mutation status of FLT3 and NRAS genes is very important because they may elicit their effects through a pathway not used by p53 protein.…”

Development of multidrug resistance due to multiple factors including P‐glycoprotein overexpression under K‐selection after MYC and HRAS oncogene activation

“…In some of them, the ploidy status is correlated with clinical outcome and/or chemoresistance. 21 In this study, MR5 and MR8 cells tended to be tetraploid under K-selection; 5 however, the DNA contents of subclones per se did not determine the response to cytotoxic drugs but might be a surrogate marker of the presence of K-selection.…”

“…drome, 21 Hodgkin lymphoma and acute lymphoblastic leukemia. In some of them, the ploidy status is correlated with clinical outcome and/or chemoresistance.…”