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Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

ABSTRACT: An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

SUBMITTER: Baliakas P

PROVIDER: S-EPMC4311230 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

Baliakas Panagiotis P Agathangelidis Andreas A Hadzidimitriou Anastasia A Sutton Lesley-Ann LA Minga Eva E Tsanousa Athina A Scarfò Lydia L Davis Zadie Z Yan Xiao-Jie XJ Shanafelt Tait T Plevova Karla K Sandberg Yorick Y Vojdeman Fie Juhl FJ Boudjogra Myriam M Tzenou Tatiana T Chatzouli Maria M Chu Charles C CC Veronese Silvio S Gardiner Anne A Mansouri Larry L Smedby Karin E KE Pedersen Lone Bredo LB Moreno Denis D Van Lom Kirsten K Giudicelli Véronique V Francova Hana Skuhrova HS Nguyen-Khac Florence F Panagiotidis Panagiotis P Juliusson Gunnar G Angelis Lefteris L Anagnostopoulos Achilles A Lefranc Marie-Paule MP Facco Monica M Trentin Livio L Catherwood Mark M Montillo Marco M Geisler Christian H CH Langerak Anton W AW Pospisilova Sarka S Chiorazzi Nicholas N Oscier David D Jelinek Diane F DF Darzentas Nikos N Belessi Chrysoula C Davi Frederic F Ghia Paolo P Rosenquist Richard R Stamatopoulos Kostas K

Blood 20141217 5

An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subs ...[more]

PMID: 25634617

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Project description:BackgroundRisks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear.ObjectivesWe estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation.MethodsA nested case-control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986-2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose.ResultsWe found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = -0.47 (95% CI: < -0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure.ConclusionsExposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

Dataset Information

Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

Publications

Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

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