Tags

Type your tag names separated by a space and hit enter

Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression.
Blood 1995; 86(6):2371-8Blood

Abstract

The translocation t(9;22) in chronic myeloid leukemia (CML) generates a bcr-abl fusion gene that codes for an aberrant chimeric mRNA. Cell lines established from CML patients in blast crisis show higher expression of this aberrant bcr-abl transcript than cells from patients in chronic phase of the disease. This observation provided the stimulus to investigate whether increased expression of the aberrant bcr-abl fusion transcript is critical to the progression of CML from chronic phase to blast crisis. We have monitored the bcr-abl mRNA expression in 25 patients by serial quantitative polymerase chain reaction analyses during a follow-up period of 12 to 156 months after diagnosis, with a median observation time of 28 months. In all patients who have shown disease progression to accelerated phase (n = 4) or blast crisis (n = 7), an increase in bcr-abl mRNA expression was detected up to 16 months before laboratory or clinical parameters showed phenotypic transformation of the malignant clone. To investigate whether the elevated levels of bcr-abl mRNA reflected an increase in the proportion of leukemic cells in the samples analyzed or primarily enhanced transcriptional activity of the bcr-abl fusion gene, we performed quantitative analyses of the bcr-abl gene at the DNA level and of the Ph chromosome at the cytogenetic level and compared these data with steady-state bcr-abl mRNA levels. We show that increased levels of the bcr-abl transcript did not reflect increased proportions of leukemic cells but elevated steady-state levels of the chimeric mRNA in the malignant cells before disease progression. Therefore, our data strongly suggest that an increase of the chimeric mRNA expression in the leukemic cells precedes the phenotypic transformation of the malignant clone.

Authors+Show Affiliations

CCRI, Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7662984

Citation

Gaiger, A, et al. "Increase of Bcr-abl Chimeric mRNA Expression in Tumor Cells of Patients With Chronic Myeloid Leukemia Precedes Disease Progression." Blood, vol. 86, no. 6, 1995, pp. 2371-8.
Gaiger A, Henn T, Hörth E, et al. Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood. 1995;86(6):2371-8.
Gaiger, A., Henn, T., Hörth, E., Geissler, K., Mitterbauer, G., Maier-Dobersberger, T., ... Lion, T. (1995). Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood, 86(6), pp. 2371-8.
Gaiger A, et al. Increase of Bcr-abl Chimeric mRNA Expression in Tumor Cells of Patients With Chronic Myeloid Leukemia Precedes Disease Progression. Blood. 1995 Sep 15;86(6):2371-8. PubMed PMID: 7662984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. AU - Gaiger,A, AU - Henn,T, AU - Hörth,E, AU - Geissler,K, AU - Mitterbauer,G, AU - Maier-Dobersberger,T, AU - Greinix,H, AU - Mannhalter,C, AU - Haas,O A, AU - Lechner,K, AU - Lion,T, PY - 1995/9/15/pubmed PY - 1995/9/15/medline PY - 1995/9/15/entrez SP - 2371 EP - 8 JF - Blood JO - Blood VL - 86 IS - 6 N2 - The translocation t(9;22) in chronic myeloid leukemia (CML) generates a bcr-abl fusion gene that codes for an aberrant chimeric mRNA. Cell lines established from CML patients in blast crisis show higher expression of this aberrant bcr-abl transcript than cells from patients in chronic phase of the disease. This observation provided the stimulus to investigate whether increased expression of the aberrant bcr-abl fusion transcript is critical to the progression of CML from chronic phase to blast crisis. We have monitored the bcr-abl mRNA expression in 25 patients by serial quantitative polymerase chain reaction analyses during a follow-up period of 12 to 156 months after diagnosis, with a median observation time of 28 months. In all patients who have shown disease progression to accelerated phase (n = 4) or blast crisis (n = 7), an increase in bcr-abl mRNA expression was detected up to 16 months before laboratory or clinical parameters showed phenotypic transformation of the malignant clone. To investigate whether the elevated levels of bcr-abl mRNA reflected an increase in the proportion of leukemic cells in the samples analyzed or primarily enhanced transcriptional activity of the bcr-abl fusion gene, we performed quantitative analyses of the bcr-abl gene at the DNA level and of the Ph chromosome at the cytogenetic level and compared these data with steady-state bcr-abl mRNA levels. We show that increased levels of the bcr-abl transcript did not reflect increased proportions of leukemic cells but elevated steady-state levels of the chimeric mRNA in the malignant cells before disease progression. Therefore, our data strongly suggest that an increase of the chimeric mRNA expression in the leukemic cells precedes the phenotypic transformation of the malignant clone. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/7662984/Increase_of_bcr_abl_chimeric_mRNA_expression_in_tumor_cells_of_patients_with_chronic_myeloid_leukemia_precedes_disease_progression_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=7662984 DB - PRIME DP - Unbound Medicine ER -