Association Between Immunoglobulin Heavy-chain Variable Region Mutational Status and Isolated Favorable Baseline Genomic Aberrations in Chronic Lymphocytic Leukemia

Overview

Journal Leuk Lymphoma

Specialties Hematology
Oncology

Date 2017 Jun 24

PMID 28641468

Citations 3

Authors

Jose D Sandoval-Sus

Julio C Chavez

Samir Dalia

Syeda Mahrukh Hussnain Naqvi

Chetasi Talati

Lisa Nodzon

Mohamed A Kharfan-Dabaja

Javier Pinilla-Ibarz

Affiliations

Soon will be listed here.

Abstract

Immunoglobulin heavy-chain variable region (IGHV) mutational status and karyotype abnormalities are important prognostic factors in chronic lymphocytic leukemia (CLL). The goal was to assess the impact of IGHV in CLL patients with isolated favorable genetic aberrations (del13q, trisomy 12, or negative fluorescence in situ hybridization [FISH]). We studied 273 CLL patients with both IGHV mutational status and cytogenetic information: 145 with isolated del13q 49 with sole trisomy 12 and 79 with negative FISH. After a median follow-up of 7.8 years, patients with del13q-unmutated IGHV had a shorter time to first treatment (TFT) (2.98 vs. 17.44 years; p < .001) and shorter overall survival (10.45 years vs. not reached; p = .0026). Patients with negative FISH-unmutated IGHV had shorter TFT (p = .02) (3.10 vs. 9.75 years, p = .053). IGHV status did not influence clinical outcomes in trisomy 12 CLL. In conclusion, IGHV mutational status shows prognostic impact in CLL patients with good prognosis genomic features.

Citing Articles

Association of Cytogenetics Aberrations and Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.

Munoz-Novas C, Gonzalez-Gascon-Y-Marin I, Figueroa I, Sanchez-Paz L, Perez-Carretero C, Quijada-Alamo M Glob Med Genet. 2024; 11(1):59-68.

PMID: 38348157 PMC: 10861322. DOI: 10.1055/s-0044-1779668.

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia.

Yun X, Zhang Y, Wang X Biomark Res. 2020; 8:40.

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Normal serum protein electrophoresis and mutated IGHV genes detect very slowly evolving chronic lymphocytic leukemia patients.

Chauzeix J, Laforet M, Deveza M, Crowther L, Marcellaud E, Derouault P Cancer Med. 2018; 7(6):2621-2628.

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References

Morilla A, Gonzalez de Castro D, Del Giudice I, Osuji N, Else M, Morilla R . Combinations of ZAP-70, CD38 and IGHV mutational status as predictors of time to first treatment in CLL. Leuk Lymphoma. 2008; 49(11):2108-15. DOI: 10.1080/10428190802360810. View

Landau D, Tausch E, Taylor-Weiner A, Stewart C, Reiter J, Bahlo J . Mutations driving CLL and their evolution in progression and relapse. Nature. 2015; 526(7574):525-30. PMC: 4815041. DOI: 10.1038/nature15395. View

Thompson P, OBrien S, Xiao L, Wang X, Burger J, Jain N . β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia. Cancer. 2015; 122(4):565-73. PMC: 4813299. DOI: 10.1002/cncr.29794. View

Rodriguez D, Bretones G, Arango J, Valdespino V, Campo E, Quesada V . Molecular pathogenesis of CLL and its evolution. Int J Hematol. 2015; 101(3):219-28. DOI: 10.1007/s12185-015-1733-0. View

Woyach J . FCR holds up to the test of time: CLL8 follow-up. Blood. 2016; 127(2):172-3. DOI: 10.1182/blood-2015-11-678557. View

Gonzalez-Gascon Y Marin I, Hernandez-Sanchez M, Rodriguez-Vicente A, Sanzo C, Aventin A, Puiggros A . A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia. Hematol Oncol. 2015; 34(2):84-92. DOI: 10.1002/hon.2196. View

. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016; 17(6):779-790. DOI: 10.1016/S1470-2045(16)30029-8. View

Hamblin T, Davis Z, Gardiner A, Oscier D, Stevenson F . Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999; 94(6):1848-54. View

Fischer K, Bahlo J, Fink A, Goede V, Herling C, Cramer P . Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2015; 127(2):208-15. DOI: 10.1182/blood-2015-06-651125. View

10.

Thompson P, Tam C, OBrien S, Wierda W, Stingo F, Plunkett W . Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2015; 127(3):303-9. PMC: 4760129. DOI: 10.1182/blood-2015-09-667675. View

11.

Sportoletti P, Baldoni S, Cavalli L, Del Papa B, Bonifacio E, Ciurnelli R . NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL. Br J Haematol. 2010; 151(4):404-6. DOI: 10.1111/j.1365-2141.2010.08368.x. View

12.

Damle R, Wasil T, Fais F, Ghiotto F, Valetto A, Allen S . Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999; 94(6):1840-7. View

13.

Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Dohner K . Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014; 123(21):3247-54. DOI: 10.1182/blood-2014-01-546150. View

14.

Shanafelt T, Geyer S, Kay N . Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL. Blood. 2003; 103(4):1202-10. DOI: 10.1182/blood-2003-07-2281. View

15.

Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L . Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2001; 343(26):1910-6. DOI: 10.1056/NEJM200012283432602. View

16.

Nabhan C, Raca G, Wang Y . Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era. JAMA Oncol. 2015; 1(7):965-74. DOI: 10.1001/jamaoncol.2015.0779. View

17.

Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J . Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med. 2011; 208(7):1389-401. PMC: 3135373. DOI: 10.1084/jem.20110921. View

18.

Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V . SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2013; 28(1):108-17. DOI: 10.1038/leu.2013.263. View

19.

Siegel R, Miller K, Jemal A . Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1):5-29. DOI: 10.3322/caac.21254. View

20.

Zelenetz A, Gordon L, Wierda W, Abramson J, Advani R, Andreadis C . Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015. J Natl Compr Canc Netw. 2015; 13(3):326-62. PMC: 4841457. DOI: 10.6004/jnccn.2015.0045. View