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 specificity of H-2 unrestricted cytotoxic T cells was analyzed in secondary CML responses. A/J strain effector cells, sensitized against A.Tlab lymphoid cells, lysed target cells from strains with differing H-2 haplotypes but all sharing Qa-1b/Tlab alleles; whereas, target cells from strains with Qa-1a/Tlaa were not. When B6.Tlaa animals were in vivo-primed and challenged in vitro with B6 stimulator cells, no cytotoxic effector cell activity was generated. However, if B6.Tlaa animals were primed in vivo with A.BY cells and then rechallenged in vitro with either A.BY or B6 stimulator cells, cytotoxic effector cells were generated that lysed target cells from strains with Qa-1b/Tlab alleles. This suggests that factors in addition to Qa/Tla may play a role in the generation of anti-Qa/Tla effector cell activity. It was also noted that targets from strains with Qa-1a/Tlaa alleles were killed, although to a much lesser extent than the Qa-1b/Tlab targets. SWR anti-DBA/1 efffector cells strongly lysed target cells frrom strains with Qa-1b/Tlab, lysed Qa-1a/Tlaa targets to a lesser extent, and produced no cytotoxic effect on B6.Tlaa target cells. These data suggest that in addition to a CML target antigen associated with Qa-1b/Tlab, there may be an additional specificity recognized by cytotoxic T cells controlled by a gene outside of Qa-1b/Tlab.
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PMID:H-2 unrestricted cytotoxic T cell activity against antigens controlled by genes in the QA/TLA region. 38 70

Irradiated mice reconstituted with bone marrow cells infected with a retrovirus carrying the bcr-abl oncogene of human chronic myeloid leukemia are subject to a range of neoplastic hematopoietic diseases, both myeloid and lymphoid. Comparison of DBA/2 and C57BL/6 mice has revealed a marked strain difference in susceptibility to the various tumor types. The present study, performed with BALB/c mice, indicates that the kinetics and nature of the induced disease can be modulated by the infection procedure, as well as the genetic background, and that retroviral regulatory sequences may influence the outcome. A distinctive clonal myeloproliferative disorder, somewhat akin to chronic myeloid leukemia but with prominent erythroid and mast cell components, as well as granulocytic excess, was characterized.
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PMID:Hematologic disease induced in BALB/c mice by a bcr-abl retrovirus is influenced by the infection conditions. 131 70

Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 X DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 X CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells.
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PMID:Allogeneic radiation chimeras respond to TNP-modified donor and host targets. 644 28

Virtually all murine plasmacytomas (MPCs) carry chromosomal translocations that juxtapose myc on chromosome 15 (chr 15) to one of the three immunoglobulin loci carrying chr 6, 12, or 16. Only some mouse strains are susceptible to MPC induction, however, with BALB/c as the outstanding example. Most other strains are resistant. Our earlier studies with reciprocal BALB/c<-->DBA/2 chimeras suggested that part of this susceptibility is determined at the level of the target cell itself (DBA/2 is MPC resistant). The probability of the Ig/myc translocation is one of the possibly relevant variables. Because MPC resistance is dominant over susceptibility, it is conceivable that the translocations prevail due to some deficiency of the Ig rearrangement or Ig-associated repair mechanisms in BALB/c cells. This could be determined at the level of the chromosomes that participate in the translocation or by genes on other chromosomes. Here, we show that the substitution of the BALB/c-derived chr 12, 6, and 15, which carry IgH, kappa, and myc, respectively, with their homologs derived from MPC-resistant mice, did not affect MPC susceptibility. The use of Robertsonian 4.12 and 6.15 chromosomes in this study has also provided us with the opportunity to assess the parental derivation of the chromosomes participating in the translocation. In contrast to the human chronic myeloid leukemia (CML)-associated BCR/ABL fusion transcript, where a strong bias was claimed that was attributed to imprinting, we have found that the parental chromosomes were randomly involved in the translocation. We have also shown that the translocations could be of uniparental or biparental origin.
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PMID:Ig/myc translocations of the plasmacytoma-prone BALB/c strain occur independently of the genetic and parental origin of the affected chromosomes 6, 12, and 15. 894 97