Chronic myelogenous leukemia (CML) is a neoplastic disorder of pluripotent hematopoietic stem cells which follows a biphasic clinical course consisting initially of a relatively benign chronic phase followed by progression to a fatal acute leukemia (CML blast crisis). A clonal cytogenetic abnormality (i.e. the Philadelphia or Ph chromosome), resulting from the reciprocal translocation t(9;22)(q34;q11), is found in over 95% of patients. A hybrid gene is created at the breakpoint of Ph, derived from the ABL proto-oncogene (9q34) and from the BCR gene (22q11), which results in the expression of a 210 KDa fusion protein tyrosine kinase called P210BCR/ABL (P210). Expression of P210 alone is generally believed to be sufficient to induce chronic phase CML but, the deregulation of additional genes appears to be required for progression to CML blast crisis, as inferred by the presence of secondary cytogenetic abnormalities in over 80% of patients. To investigate the potential significance of P210 expression in the induction of genetic instability associated with CML progression, I studied cytogenetic changes in a murine cell line (32D) which expressed P210BCR/ABL from a retroviral vector. Using Giemsa-trypsin banding technique, I found a common marker chromosome t(4;12) in 13 subclones, a second new marker t(2;17) in 3/13 subclones and, additional clonal marker chromosomes in all of the subclones examined. Six subclones consisted of two or three karyotypically distinct cell populations. This study demonstrates that BCR/ABL can directly induce both numerical and structural chromosomal abnormalities in hematopoietic cells. This murine cell model may provide a useful tool to further study the causal relationship of cytogenetic instability and cooperative molecular events involved in the initiation and progression of CML.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.26154 |
| Date | January 1994 |
| Creators | Sun, Guoxian |
| Contributors | Cooper, B. A. (advisor), Laneuville, P. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397420, proquestno: MM94530, Theses scanned by UMI/ProQuest. |
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