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MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study
- Source :
- Blood, Blood, American Society of Hematology, 2015, 126 (22), pp.2466-2474. ⟨10.1182/blood-2015-05-647602⟩
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- Diffuse Large B-Cell lymphoma (DLBCL) with MYC rearrangement ( MYC -R) carries an unfavorable outcome. We explored the prognostic value of MYC translocation partner gene in a series of MYC -R de novo DLBCL patients enrolled in first-line prospective clinical trials of the GELA/LYSA and treated with rituximab-anthracyclin-based chemotherapy. Seven hundred seventy four DLBCL cases characterized for cell of origin by the Hans classifier were analysed using fluorescence in situ hybridization (FISH) with BCL2 , BCL6 , MYC , IGK , IGL breakapart and IGH/MYC , IGK/MYC , IGL/MYC fusion probes. MYC rearrangement ( MYC -R) was observed in 51/574 (8.9%) evaluable DLBCL. MYC -R cases were predominantly of germinal centre B-cell-like subtype 37/51(74%) with no distinctive morphological and phenotypic features. Nineteen were MYC single-hit ( MYC -SH) and 32 MYC double-hit ( MYC -DH) ( MYC plus BCL2 and/or BCL6 ) DLBCL. MYC translocation partner was an immunoglobulin gene in 24 cases ( MYC-IG ) and a non-immunoglobulin gene ( MYC-non-IG ) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) ( P=.0002 ) compared to MYC -negative patients, whereas no survival difference was observed between MYC-non-IG and MYC -negative patients. In multivariate analyses MYC-IG predicted poor PFS ( P=.0051 ) and OS ( P=.0006 ) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC rearrangement is correlated to MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC rearrangement who should be routinely characterized according to MYC partner gene. Trials are individually registered with www.ClinicalTrials.gov numbers NCT00144807, NCT01087424, NCT00169143, NCT00144755, NCT00140660, NCT00140595 and NCT00135499.
- Subjects :
- Adult
Male
Immunoglobulin gene
Adolescent
[SDV]Life Sciences [q-bio]
Immunology
Immunoglobulins
Chromosomal translocation
Biology
Biochemistry
Disease-Free Survival
Translocation, Genetic
Proto-Oncogene Proteins c-myc
Antibodies, Monoclonal, Murine-Derived
03 medical and health sciences
0302 clinical medicine
International Prognostic Index
immune system diseases
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Cyclophosphamide
Survival rate
ComputingMilieux_MISCELLANEOUS
Aged
030304 developmental biology
Aged, 80 and over
Gene Rearrangement
0303 health sciences
Cell Biology
Hematology
Gene rearrangement
Middle Aged
medicine.disease
BCL6
3. Good health
Lymphoma
Survival Rate
Doxorubicin
Vincristine
030220 oncology & carcinogenesis
Cancer research
Prednisone
Female
Lymphoma, Large B-Cell, Diffuse
Rituximab
Diffuse large B-cell lymphoma
Subjects
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Database :
- OpenAIRE
- Journal :
- Blood, Blood, American Society of Hematology, 2015, 126 (22), pp.2466-2474. ⟨10.1182/blood-2015-05-647602⟩
- Accession number :
- edsair.doi.dedup.....b12959a8eb9e1fc8278d6f86b8273a97