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)

The relationship between activation of the N-RAS gene and the leukemic progression of undifferentiated chronic myeloproliferative disease (UCMPD) was investigated in a 71-year-old male. Hematologically, it was difficult to differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR rearrangement (BCR-) either at the beginning or in the terminal stages of the disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular analysis, using the polymerase chain reaction (PCR) and direct sequencing. The DNA of leukemic cells at the beginning of the leukemic progression did not show any abnormalities, but at the terminal stage of the disease the DNA showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon 13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These observations suggest that the activated N-RAS gene contributes to the hematologic progression of UCMPD.
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PMID:N-RAS activation in the terminal stage of undifferentiated chronic myeloproliferative disease. 139 9

In an attempt to identify novel mHas that induce GVL effect on chronic myeloid leukemia (CML), we analyzed peripheral blood T cells of 4 CML patients who relapsed after allogeneic stem cell transplantation and received donor leukocyte infusion (DLI), for the presence of antigen-specific T-cell proliferation. When peripheral blood lymphocyte collected from patients every 2-4 weeks after DLI were subjected to complementarity determining region (CDR) 3 size distribution analysis of T-cell receptor beta chain, clonal proliferation of a limited number of CD4+ T cells was detected in all patients 2-4 months after DLI in association with the occurrence of GVL effect. To identify an epitope of the T-cell clone that probably mediates GVL effect, we determined nucleotide sequence of CDR3 of the T cells and screened the database for the presence of T cells with a CDR3 sequence similar to that of the GVL-mediating T cells. In one of 4 patients who showed clonal proliferation of a BV16+ T cell, a CDR3 motif QDR was shared by a T-cell clone that recognized an 85-99 peptide of myelin basic protein presented by HLA-DRB1*1501. When the I domain of CD49b, a candidate peptides that could bind to this CDR3 motif in the context of DRB1*1501, was studied, codon 256 in the I domain of the recipient was ATT (Ile) while that of the donor was GTT (Val). The BV16+ T cells showed proliferative response to DRB1*1501 L-cell transfectant pulsed with the recipient type CD49b. Thus, identification of a clonotype of T cells that mediate GVL effect in patients receiving DLI and a search for T-cell clones with a similar clonotype to the GVL-mediating T cells followed by screening of polymorphic peptides that could stimulate the T cells appears to be useful in identifying novel mHas serving a target antigens of GVL effect.
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PMID:Identification of novel minor histocompatibility antigens responsible for graft-versus-leukemia (GVL) effect on chronic myeloid leukemia: usefulness of determining the clonotype of T cells associated with GVL effect after donor leukocyte infusion. 1243 Aug 63