Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.
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PMID:BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). 1206 77

The effect of imatinib on myeloproliferative disease in transgenic (Tg) mice expressing the P230 BCR/ABL transcript is unknown. To investigate this issue, we administered imatinib (30 mg/kg per day) orally to P230 BCR/ABL-expressing Tg mice for 30 days. Following imatinib administration, the enlarged spleen was significantly reduced to within the normal size range. Infiltrating megakaryocytes in the long-axis section of the spleen were also significantly reduced. However, the cellularity of the bone marrow was not affected. Fluorescence-activated cell-sorting analysis revealed that infiltrating mature granulocytes in the spleen were reduced in number. The numbers of infiltrating CD34, CD117, CD61, and CD11b populations were also reduced in immature populations of the spleen. Real-time quantitative polymerase chain reaction analysis of messenger RNA revealed a dramatic reduction in the p230 BCR/ABL transcript for CD34, CD117, CD61, and CD11b populations in both bone marrow cells and spleen cells. Western blotting and immunoprecipitation analysis also revealed a marked reduction in P230 BCR/ABL protein expression in both bone marrow cells and spleen cells. Thus, imatinib administration had the intriguing effect of replacing clones with high expression of p230 BCR/ABL complementary DNA with clones with very low expression. These data show that imatinib may still be capable of eliminating and eradicating clones with high p230 BCR/ABL expression and healing the disease phenotype in Tg mice. Pluripotent clones with very low p230 BCR/ABL expression still survive as immature CD34, CD117, CD61, and CD11b populations.
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PMID:Oral administration of imatinib to P230 BCR/ABL-expressing transgenic mice changes clones with high BCR/ABL complementary DNA expression into those with low expression. 1711 62