Characterisation of hairy cell leukaemia by tiling resolution array‐based comparative Genome hybridisation: a series of 13 cases and review of the literature

Abstract

Little is known about the cytogenetic features and molecular mechanisms behind hairy cell leukaemia (HCL), despite the advances in diagnosis and treatment. Therefore, we used high-resolution genome-wide array-based comparative genomic hybridisation (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) to characterise copy number alterations (CNAs) in DNA from 13 cases of HCL. We also summarise CNAs and cytogenetic features in 109 HCL cases comprising our 13 cases and 96 cases from the literature. Genomic array-CGH revealed imbalances in two out of 13 cases in addition to previously described copy number variants (CNVs) found in healthy individuals. In one case, a 700 kb deletion of 20q11.22 was detected encompassing ten characterised genes, among them the TP53INP2, DNCL2A and ITCH genes. In the second case, trisomy 5, and a deletion of 5p15.2 encompassing a non-characterised gene AY328033 was found. Altogether only 20/81 (25%) of all cases studied by CGH or gene dose array revealed CNAs. The most common recurrent deletions and breakpoints were 14q22-32 (33%), 6q25 (16%), 2p12 (10%), 22q11 (10%), 17p11-13 (10%), 7q32-36 (9%), 18q11-13 (7%), 1q32-44 (6%), 8p22-23 (6%) and 7q11 (6%). Trisomy 5 occurred in 15%. In addition, several other recurrent breakpoints were identified. Although a number of genomic imbalances were identified in the HCL samples, the genome appeared remarkably stable.

De novo hairy cell leukemia with a major BCR/ABL1 rearrangement: A case report with a literature review

“…The most possible hypothesis for our case is that a small population of HCL clones acquired additional genetic aberration of BCR/ABL1 . This assumption is supported by one case report that HCL cells occasionally showed deletions at 22q11.2 . For evidence of the lymphoid cells with BCR/ABL1 translocation, a high incidence (30%) of BCR/ABL1 translocation was also observed in biphenotypic acute leukemia .…”

“…This assumption is supported by one case report that HCL cells occasionally showed deletions at 22q11.2. 12 For evidence of the lymphoid cells with BCR/ABL1 translocation, a high incidence (30%) of BCR/ABL1 translocation was also observed in biphenotypic acute leukemia. 13 In addition, it has been documented that various fractions of mature B cells belong to the leukemic compartment and are Ph+ CML.…”

Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation

“…Alternative splicing of DOR by heterogenous ribonucleoprotein A2 promotes ovarian cancer cell migration and invasion (31). A 700-kb deletion of chromosome 20 encompassing DOR was detected in hairy cell leukemia patients (32). In Drosophila melanogaster, DOR acts as a coactivator for ecdysone receptor (10).…”

NFkB is activated by multiple mechanisms in hairy cell leukemia

“…additional to those consistently reported for HCL hitherto [Ostergaard et al, 2001;Andersen et al, 2004;Nordgren et al, 2010]. Second, to identify gene targets of chromosomal aberrations, we performed genomic profiling of MLMA using Cytoscan HD arrays from Affymetrix which allow assignment of CNVs and the underlying gene candidates at high resolution.…”

“…Generally, HCL cells show few chromosomal abnormalities and thus far no recurrent rearrangement has been described. The most frequent aberrations include genomic gains located at 5q and losses at 7q (Ostergaard et al, ; Andersen et al, ; Nordgren et al, ).…”