Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the polymerase chain reaction and Southern blot analysis the expression was detected of a bcr-abl mRNA lacking abl exon a2. This was due to a corresponding unusual localization of the breakpoint in the c-abl gene and was seen in a patient with Philadelphia (Ph) chromosome positive chronic myelogeneous leukemia in chronic phase. This type of mRNA has been described only once before in two Ph-positive acute lymphoblastic leukemia patients, by Soekarman et al. (1). The abl exon a2 sequences, which are missing in the three reported patients, code for a part of the SH3 region of the abl protein, which is supposed to be involved in negative regulation of the kinase domain. The clinical significance of this finding is discussed.
Leukemia 1991 Jun
PMID:bcr-abl mRNA lacking abl exon a2 detected by polymerase chain reaction in a chronic myelogeneous leukemia patient. 793 77

Constitutive activation of BCR-ABL tyrosine kinase fusion protein has been shown to be an essential step in the pathogenesis of Philadelphia chromosome (Ph)-positive leukemias. We studied the tyrosine phosphorylated proteins which might be involved in the signaling pathway p185BCR-ABL using a Ph-positive acute lymphoblastic leukemia cell line. p185BCR-ABL but not p145c-abl was constitutively phosphorylated on tyrosine in this cell line. p21ras GTPase-activating protein (GAP) was physically associated with p185BCR-ABL, but not with p145c-abl, and GAP-associated proteins p62/p190 were found to be tyrosine-phosphorylated. Furthermore, p185BCR-ABL was also physically associated with phospholipase C-gamma 1 (PLC-gamma) and phosphatidylinositol 3'-kinase (P13-kinase). Concomitantly, both PLC-gamma and p85 subunit of P13-kinase are tyrosine-phosphorylated in the cells with p185BCR-ABL. These data suggest that GAP, GAP-associated proteins, PLC-gamma, and P13-kinase may participate in downstream signaling for p185BCR-ABL tyrosine kinase.
Leukemia 1994 Jan
PMID:Potential molecules implicated in downstream signaling pathways of p185BCR-ABL in Ph+ ALL involve GTPase-activating protein, phospholipase C-gamma 1, and phosphatidylinositol 3'-kinase. 828 76

In human Ph-positive leukemia there is a clear association of different forms of the BCR-ABL oncogene with distinct types of leukemia. The P190 form of BCR-ABL is rarely observed in chronic myeloid leukemia (CML) but is present in 50% of Ph-positive acute lymphoblastic leukemia (ALL). In contrast, the P210 form is observed both in CML and 50% of Ph-positive ALL. Methylation of the proximal promoter of the ABL1 gene has been shown to be a nearly universal event associated with clinical progression of CML. This raises the question of whether methylation of the ABL1 promoter is an epigenetic modification also associated with Ph-positive ALL. To study this issue, we used methylation-specific PCR and bisulfite sequencing to determine the methylation status of the ABL1 promoter in 18 Ph-positive ALL samples. We report here that gene-specific ABL1 promoter methylation is associated mainly with the P210 form of BCR-ABL and not the P190 form. While six out of the seven P210-positive ALL samples had ABL1 promoter methylation, none of the 11 P190-positive ALL samples demonstrated ABL1 promoter methylation. In addition, we estimated the extent and relative abundance of ABL1 promoter methylation in several Ph-positive ALL samples and compared it to the methylation pattern in chronic, accelerated and blastic crisis phases of CML. We put forth a model that correlates the different types of leukemias with the different levels of ABL1 promoter methylation.
Leukemia 2001 Apr
PMID:ABL1 methylation in Ph-positive ALL is exclusively associated with the P210 form of BCR-ABL. 1136 59

The patient was a 68-year-old woman who was diagnosed as having Ph-positive acute lymphoblastic leukemia (ALL). Complete remission (CR) was not obtained with the induction therapy of the Japan Adult Leukemia Study Group Protocol. We then considered administration of imatinib (ST1571). The institutional review board of our hospital approved this therapy, and we initiated the administration of imatinib 400 mg/day after obtaining written informed consent from the patient. At day 10 of the regimen, CR was achieved, treatment had to be discontinued RT-PCR showed no induction of detectable minor bcr-abl mRNA after three courses of consolidation chemotherapy combined with imatinib. We changed the administration protocol of Imatinib to two weeks out of every in four, weeks, and conducted 9 courses of consolidation chemotherapy. The negative result of RT-PCR has been maintained 10 months after diagnosis. The adverse effects were body weight gain and retaining pleural effusion, and these were controlled by the diuretics. The negative result of RT-PCR in Ph positive ALL after chemotherapy has rarely been reported, so the combination of imatinib and chemotherapy may be considered to be effective for Ph positive ALL.
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PMID:[Successful induction and long-term molecular remission with imatinib mesylate and chemotherapy in a case of Ph-positive acute lymphoblastic leukemia]. 1282 9