Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

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Authors	BALIAKAS P. MOYSIADIS T. HADZIDIMITRIOU A. XOCHELLI A. JEROMIN S. AGATHANGELIDIS A. MATTSSON M. SUTTON L.A. MINGA E. SCARFO L. ROSSI D. DAVIS Z. VILLAMOR N. PARKER H. KOTAŠKOVÁ Jana STALIKA E. PLEVOVÁ Karla MANSOURI L. CORTESE D. NAVARRO A. DELGADO J. LARRAYOZ M. YOUNG E. ANAGNOSTOPOULOS A. SMEDBY K.E. JULIUSSON G. SHEEHY O. CATHERWOOD M. STREFFORD J.C. STAVROYIANNI N. BELESSI C. POSPÍŠILOVÁ Šárka OSCIER D. GAIDANO G. CAMPO E. HAFERLACH C. GHIA P. ROSENQUIST R. STAMATOPOULOS K.
Year of publication	2019
Type	Article in Periodical
Magazine / Source	haematologica
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://www.haematologica.org/content/haematol/104/2/360.full.pdf
Doi	http://dx.doi.org/10.3324/haematol.2018.195032
Keywords	PREVIOUSLY UNTREATED PATIENTS; B-CELL RECEPTORS; STEREOTYPED IGHV3-21; GENOMIC ABERRATIONS; CLL; MUTATIONS; SURVIVAL; INDEX; GENE; CLASSIFICATION
Description	Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.
Related projects:	Analýza klonální heterogenity chronické lymfocytární leukemie pomoci sekvenování nové generace genu pro B-buněčný receptor. Národní studie MEDGENET - Medical genomics and epigenomics network CEITEC 2020