Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cytotoxic monoclonal antibody, CALL1, produced against a human schwannoma tumor was found to react with human platelets, common acute lymphocytic cells (cALL), and lymphoblasts from lymphoid blast crisis of chronic myelocytic leukemia (CML). The hybridoma was repeatedly cloned, and the antibody was considered reactive to a single antigen by absorption tests demonstrating that platelets remove cALL activity and cALL cells absorb platelet activity from the antibody. In addition, chromatofocusing showed that the antibody against platelets and cALL had the same isoelectric point. The CALL1 antibody bound to megakaryocytes but inhibited neither myeloid (CFU-C) nor erythroid (BFU-E) colony formation from bone marrow stem cells. Immunoprecipitation and SDS-gel electrophoresis indicated that CALL1 reacts with a polypeptide of 26,000 daltons.
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PMID:A monoclonal antibody cross-reactive with human platelets, megakaryocytes, and common acute lymphocytic leukemia cells. 618 94

The 22nd chromosome is known mainly due to chromosome (Philadelphia) which is its derivative-a typical cytogenetic sign of chronic myeloid leukaemia (CML). The molecular genetic finding in these patients is the fused gene which developed by combination of the 3' part of the oncogene ABL from chromosome 9 and 5' part of the gene which developed by combination of the 3' part of the oncogene ABL from chromosome 9 and 5' part of the BCR "gene". The product of the gene retains the original kinase activity (ABL) which is even higher. Detection of BCR/ABL is an important diagnostic aid whic makes it possible to investigate residual diseases in patients after intensive treatment and transplantation of bone marrow and early detection of possible relapses. Among locuses of the 22nd chromosome the author mentions also the locus of the second one of the light immunoglobulin chains-lambda, incl. some of its "related" genes, the group of crystalline locuses (CRYB), the locus of the beta-chain of the GM-CSF receptor, the myoglobin locus (MB) and finally locus NF2 of central neurofibromatosis-bilateral neurinoma of the acoustic nerve.
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PMID:[The human genome--chromosome 22]. 859 11

Schwannomas, although benign, can be fatal or give rise to significant morbidity due to an unpredictable growth rate. They can reoccur after surgery or radiation, current treatments each with significant inherent risks. These risks are further amplified in neurofibromatosis type 2 (NF2), a germ line predisposition syndrome characterized by multiple schwannomas, underlying the need for biological targeted therapies. Gleevec (STI571, imatinib mesylate), in addition to the bcr-abl oncogene in chronic myelogenous leukemia, inhibits c-kit and platelet-derived growth factor receptor (PDGFR) signaling, thereby expanding its use to several malignant and benign human diseases. In the present study, we show that human sporadic and NF2-associated schwannomas have increased expression along with activation of PDGFR-alpha, PDGFR-beta, and c-kit receptors, compared with normal or traumatic nerve. Using the human NF2-null HEI-193 schwannoma cell line, Gleevec inhibited schwannoma viability, proliferation, and anchorage-independent growth, as well as induced apoptosis in a dose-dependent manner (IC(50) 5-10 micromol/L). These antitumorigenic effects were correlated to inhibition of PDGFR-alpha, PDGFR-beta, and c-kit activation/phosphorylation and major downstream signaling pathways. Lack of robust xenograft or transgenic models of schwannomas prevents extension of these studies in vivo. However, the established long track record and tolerable toxicity of Gleevec already in clinical use and our preclinical data lead us to propose that Gleevec should be evaluated in human schwannomas with shown progressive growth.
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PMID:Human schwannomas express activated platelet-derived growth factor receptors and c-kit and are growth inhibited by Gleevec (Imatinib Mesylate). 1950 33