Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2.

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Authors	STREFFORD JC. SUTTON LA. BALIAKAS P. AGATHANGELIDIS A. MALČÍKOVÁ Jitka PLEVOVÁ Karla SCARFO L. DAVIS Z. STALIKA E. CORTESE D. CAHILL N. PEDERSEN LB. DI CELLE PF. TZENOU T. GEISLER C. PANAGIOTIDIS P. LANGERAK AW. CHIORAZZI N. POSPÍŠILOVÁ Šárka OSCIER D. DAVI F. BELESSI C. MANSOURI L. GHIA P. STAMATOPOULOS K. ROSENQUIST R.
Year of publication	2013
Type	Article in Periodical
Magazine / Source	Leukemia
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://www.ncbi.nlm.nih.gov/pubmed/23558524
Doi	http://dx.doi.org/10.1038/leu.2013.98
Field	Oncology and hematology
Keywords	chronic lymphocytic leukemia; immunoglobulin genes; stereotyped B-cell receptors; NOTCH1 mutations; SF3B1 mutations
Attached files	EL_1138694_Distinct_patterns.pdf Strefford.pdf
Description	Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset #1, #2 and #8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset #2 (44%) versus subset #1 and #8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%, lower than the frequency observed in either subset #1 or #8 (19% and 14%, respectively; P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy.
Related projects:	SuPReMMe - Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny CEITEC - Central European Institute of Technology Molekulární charakterizace B buněčných receptorů a jejich vztah k evoluci genetických změn u chronické lymfocytární leukémie