Twenty patients had chronic myeloid leukemia in blast crisis (CML-BC), three had Ph+ de novo acute nonlymphocytic leukemia (ANLL), and five had de novo acute lymphoblastic leukemia (ALL).
To study the possible involvement of T lymphocytes in Philadelphia chromosome (Ph)-positive chronic myelocytic leukemia (CML) we analyzed the arrangement of the bcr gene in T cell and non-T cell samples of 12 CML patients.
The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes.
The translocation of the c-abl oncogene from chromosome 9 to the bcr gene on chromosome 22 in cases of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) generates an aberrant bcr-abl fusion transcript which may be intimately related to the pathogenesis of CML.
Nineteen of 21 patients with chronic myelogenous leukemia (CML) possessed a chromosomal break within the 5.8 kilobase (kb) breakpoint cluster region (bcr).
Rearrangement of the breakpoint cluster region (bcr) was detected in 11 of the 23 patients with Ph-negative CML (48 percent), indicating the presence of the abnormal molecular events in Ph-positive CML without documentation of the Ph cytogenetic abnormality.
As expected, approximately half of the Ph' positive acute leukemias showed a breakpoint on chromosome 22 falling outside the "breakpoint cluster region" (bcr) known to be involved in CML.
In a phase II study, patients with chronic myelogenous leukemia in blast crisis (CML-BC) were treated with intravenous (IV) mitoxantrone (5 mg/m2 per day given over 30 min x 5 days and high-dose arabinosylcytosine (ara-C) (3 g/m2 IV q 12 h x 6).
Thus, the genomic breakpoint in this patient must lie upstream of the BCR defined by study of Ph-positive CML and downstream of the C-lambda gene locus.
Philadelphia (Ph1) chromosome breakpoints in acute lymphoblastic leukemia (ALL) are of two kinds: those within the breakpoint cluster region (bcr+), as in chronic myeloid leukemia (CML), and those outside it (bcr-).
Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr).
The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML) contains sequences from chromosome 9, including the ABL protooncogene, that have been translocated to the breakpoint cluster region (bcr) of chromosome 22, giving rise to a bcr-ABL fusion gene, whose product has been implicated in the genesis of CML.
Southern blot analysis showed that the Ph translocation did not involve the 5.8-kilobase breakpoint cluster region segment characteristically seen in CML.
In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity.
The blast cell population of 60 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were analyzed with a panel of monoclonal antibodies to determine the cell surface antigen phenotypes.
The breakpoint on chromosome 22 is located within the BCR gene: in CML, breakpoints are clustered within 5.8 kb of DNA, the major breakpoint cluster region (Mbcr).
Philadelphia (Ph) chromosome negative chronic myeloid leukemia (CML) can be distinguished from clinically similar disorders on the basis of the presence of rearrangement of the breakpoint cluster region (bcr) of chromosome 22.
Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy.