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Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib.
- Source :
-
Haematologica [Haematologica] 2014 Sep; Vol. 99 (9), pp. 1441-7. Date of Electronic Publication: 2014 May 16. - Publication Year :
- 2014
-
Abstract
- The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874).<br /> (Copyright© Ferrata Storti Foundation.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Alternative Splicing
Blood Platelets drug effects
Blood Platelets pathology
Drug Monitoring
Female
Fusion Proteins, bcr-abl metabolism
Genotype
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Leukocytes drug effects
Leukocytes pathology
Male
Middle Aged
Phenotype
RNA, Messenger metabolism
Remission Induction
Survival Analysis
Treatment Outcome
Antineoplastic Agents therapeutic use
Benzamides therapeutic use
Fusion Proteins, bcr-abl genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Piperazines therapeutic use
Pyrimidines therapeutic use
RNA, Messenger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 99
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 24837466
- Full Text :
- https://doi.org/10.3324/haematol.2013.096537