Prospective multicentric molecular study for poor prognosis fusion transcripts at diagnosis in adult ALL patients - The LALA94 experience
| Autor: | Denis Fiere, Frederic Davi, Jean-Michel Cayuela, Elizabeth Macintyre, Marina Lafage, Dominique Bories, Christian Bastard, Hervé Dombret, Christophe Picard, Claude Boucheix, Sandrine Hayette, Thierry Fest, Madeleine Dupont, Marie-Pierre Gaub, Christelle Bilhou-Nabera, Véronique Lhéritier, Xavier Thomas, Sophie Raynaud, Jean-Paul Vaerman, C. Charrin, Jean Gabert, Claude Preudhomme, Nicole Frenoy, Nicole Dastugue |
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| Předmět: |
Oncology
medicine.medical_specialty Pediatrics Randomization medicine.drug_class business.industry medicine.medical_treatment Immunology Chromosomal translocation Cell Biology Hematology medicine.disease Molecular Abnormality Biochemistry Tyrosine-kinase inhibitor Targeted therapy Fusion gene hemic and lymphatic diseases Acute lymphocytic leukemia Internal medicine Epidemiology medicine business |
| Zdroj: | ResearcherID |
| Popis: | From 1994 to 2000, 984 adults aged from 15 to 55 years with newly diagnosed Acute Lymphoblastic Leukemia (ALL) were eligible for randomization in the multicentric LALA-94 clinical protocol. The t(9;22), t(1;19) and t(4;11) translocations corresponding to BCR-ABL, E2A-PBX1 and MLL-AF4 fusion gene transcripts respectively, were considered as independent poor prognostic factors. Standardized RT-PCR analysis of these fusion gene transcripts were performed by 17 laboratories in order to provide data before the second randomization (J35) on 787 patients. In this multicentric study, validated data were available for therapeutic stratification for 91% of these analysed patients. No false positive RT-PCR was reported. Secondarily to retrospective BCR-ABL FISH, few false BCR-ABL negative RT-PCR were identified, leading to the design of new BIOMED-1 primers for b3-a3 junctions detection. Moreover, the LALA-94 study allowed to define new guidelines for molecular analysis at diagnosis. Like in other studies, the BCR-ABL transcript was found to be the most frequent molecular abnormality in B-ALL (24%) whereas MLL-AF4 and E2A-PBX1 were detected in 5% and 3.5% of B-ALL, respectively. Epidemiological and clinical data of MLL-AF4 and E2A-PBX1 were concordant with previous publications. Interestingly, because of the large number of reviewed patients, the different BCR-ABL subtypes (M-BCR and m-BCR) were statistically characterized by few clinical data. M-BCR subgroups had a higher age than m-BCR (p= 0.016) and occurs especially during the second semester (p= 0.034). Moreover, the comparison of clinical data at diagnosis of M-BCR variants showed that median age of b3a2 was statistically younger than b2a2 (p= 0.04) and that b3a2 occurs more frequently in man (p= 0.02). For the first time, these data suggest that these BCR-ABL breakpoints: m-BCR and M-BCR and also b2a2 and b2a3, are secondary to different physio-oncologic mechanisms even if therapeutic regimens including the same targeted therapy (tyrosine kinase inhibitor) for all BCR-ABL variants is the rule today. |
| Databáze: | OpenAIRE |
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