We therefore sought evidence for analogous point mutations in the ABL gene in patients with Ph-negative, BCR-negative CML (n = 25), Ph-negative ALL (n = 18) and in Ph-positive CML in transformation (n = 28).
Approximately five percent of pediatric acute lymphoblastic leukemias (ALL) contain a translocation (9;22)(q34;q11) which results in rearrangement of the bcr and abl genes.
In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis.
Detection of BCR/ABL translocation by polymerase chain reaction in leukemic progenitor cells (ALL-CFU) from patients with acute lymphoblastic leukemia (ALL).
We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL).
The ABL oncogene is consistently rearranged and activated as a consequence of the translocation t(9;22) that gives rise to the Philadelphia chromosome in chronic myeloid leukemia and in some cases of acute lymphoblastic leukemia.
In lymphoblastic leukemias, there are two molecular subtypes of the Ph1 chromosome, one with a rearrangement of the breakpoint cluster region (bcr) of the BCR gene, producing the same 8.5-kilobase BCR-ABL fusion mRNA seen in chronic myelogenous leukemia (CML), and the other, without a bcr rearrangement, producing a 7.0-kilobase BCR-ABL fusion mRNA that is seen only in acute lymphoblastic leukemia (ALL).
The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia.
The findings suggested two distinct subtypes of ALL: one defined by t(9;22)(q34;q11) and expression of P185BCR-ABL tyrosine kinase and one with variant karyotypes and no P185BCR-ABL expression.
This results in an 8.7-kilobase mRNA that encodes the P210 BCR-ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7.0-kilobase mRNA that produces the P185 BCR-ABL gene product found in most Philadelphia chromosome-positive patients with acute lymphocytic leukemia.
Thus, the order of loci on chromosome 22 is centromere----BCR2, BCR4, and IGL----BCR1----BCR3----SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph1 chromosome.
The role of ABL on the Philadelphia chromosome in acute lymphoblastic leukemia is only now beginning to be understood, but is likely to be similar, and a new ABL species has already been identified by several groups.
This observation also confirmed that, as in de novo Ph1-positive ALL, both the P190 and P210 varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph1.
Analysis of the functions of these new molecules may provide insight into mechanisms by which oncogenic abl proteins participate in the etiology of CML and ALL.
Alternative chimeric proteins, p210BCR-ABL and p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively.
Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization.
In the present study, three chronic myelogenous leukemia (CML) patients with variant Philadelphia (Ph) chromosomes (complex types), two CML patients with a masked Ph, one case with Ph positive acute lymphocytic leukemia (ALL), and one with Ph positive acute myelocytic leukemia (AML) were analyzed by standard cytogenetic techniques (G-banding), Southern blot studies, and fluorescence in situ hybridization (FISH) procedures using probes from portions of the bcr and abl genes.