Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of the Y chromosome with a resulting 45, X0 karyotype is observed in normal bone marrow cells of elderly males but also in haematological malignancies. Whether Y loss in neoplastic cells is related to the process seen in normal ageing or is part of the carcinogenic process is unknown. The present study concerns the cytogenetic data from 1907 consecutive leukaemic or preleukaemic male patients with special regard to the presence or absence of the Y chromosome. Sixty-five patients (3.4%) had a 45, X-Y clone in their bone marrow (BM) cells. Loss of Y was rare below the age of 50 but increased in older patients, reaching 25% of the men over 80. Sixteen patients (0.08%) had more than 90% X0 cells in their BM. A correlation between Y loss and leukaemia could be established in seven cases, three of which were acute myeloid leukaemia M2 subtype where -Y is known to be a secondary event. In three other cases, -Y was part of a complex karyotype. Only one patient exhibited a 45, X0 karyotype, with no other rearrangement, that could be positively correlated with the neoplastic process.
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PMID:Loss of the Y chromosome in bone marrow cells: results on 1907 consecutive cases of leukaemia and preleukaemia. 1019 58

Using in situ hybridization with an X and Y chromosome probe mixture, 106 bone marrow samples from 38 patients with malignant and non-malignant hematological diseases who received sex-mismatched allogeneic hematopoietic progenitor cell transplants (PCT) in a single institution within short-term intervals (1, 3, 6, 12, 24 and >24 months) have been sequentially studied. The patients received either HLA-identical (n = 31) or non-identical (n = 7) PCT. Twenty-six children showed donor chimerism, 10 children showed mixed chimerism (MC) and two children presented autologous reconstitution. Chimerism status with different parameters has been related (age, sex, donor, disease status before PCT, conditioning regimen, GVHD prophylaxis, relapse, GVHD and survival). Our results indicate that female patients (P = 0.011) and a less intensive conditioning regimen (P = 0.039) are significantly associated with the MC status. Mixed chimerism is not, per se, significantly associated with leukemia relapse but an increase of the MC is indicative of clinical relapse.
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PMID:Follow-up of chimerism in children with hematological diseases after allogeneic hematopoietic progenitor cell transplants. 1043 40

In the interpretation of the varied and complex cytogenetic counts obtained in analysis of bone marrow (BM) samples for leukemia, loss or gain of certain chromosomes may or may not be significant for prognosis. Loss of the Y chromosome in elderly males is a benign finding. Trisomy 15 is rare and may represent another age-related abnormality, particularly in males, together with -Y. We reviewed 3,242 routine referrals sent to our laboratory for BM cytogenetics, over a period of 34 months. We detected 5 cases with uncomplicated trisomy 15, 3 in males and 2 in females. Three of these patients had the diagnosis of myelodysplastic syndrome (MDS). All 3 males showed a -Y cell line, although the 2 females did not have an X chromosome loss. All 5 patients were alive and well at times varying from 12 months to 4 years post-diagnosis. In the further analysis of our referral cohort, there were 62 males with loss of the Y chromosome as the sole abnormality, and of these 47 (76%), were referred with myeloid disease. The frequency of trisomy 15 in our laboratory was 1/475 referrals, but 1/292 in successful cultures from new patients. This is the first report providing frequency data for trisomy 15. Further data with longer term follow-up is required to establish the significance of trisomy 15 in elderly leukemic patients.
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PMID:Frequency of trisomy 15 and loss of the Y chromosome in adult leukemia. 1054 65

We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with > 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if > 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable. Genes Chromosomes Cancer 27:11-16, 2000.
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PMID:Clinical significance of Y chromosome loss in hematologic disease. 1056 81

Minor or histocompatibility (H) antigens are recognized by CD4+ and CD8+ T lymphocytes as short polymorphic peptides associated with MHC molecules. They are the targets of graft versus host and graft versus leukemia responses following bone marrow transplantation between HLA-identical siblings. Several genes encoding class I-restricted minor H epitopes have been identified, but approaches used for these have proved difficult to adapt for cloning class II-restricted minor H genes. We have combined the unique antigen-presenting properties of dendritic cells and high levels of episomal expression following transfection of COS cells to identify a Y chromosome gene encoding two HY peptide epitopes, HYAb and HYEk.
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PMID:Dendritic cells permit identification of genes encoding MHC class II-restricted epitopes of transplantation antigens. 1089 70

Genes controlling both testis determining and expression of the male-specific transplantation antigen, HY, are located on the short arm of the mouse Y chromosome, and on the X and Y-linked translocation, Sxr(a). A mutation of Sxr(a) was discovered in a cross between an Sxr carrier male and a T16H/X female. This was designated Sxr(b) and found to affect both the expression of HY and spermatogenesis, but not testis differentiation, thereby disproving Ohno's hypothesis that HY controlled testis determination. Molecular genetic analysis showed the mutation to be caused by fusion of two duplicated genes, Zfy1 and Zfy2, deleting the intervening DNA. This deletion interval, deltaSxr(b), contained a number of genes, each a candidate HY gene. Expression cloning with HY-specific T cell clones identified Smcy, Uty and Dby as encoding peptide epitopes of this transplantation antigen. The human homologues SMCY and UTY likewise express HY antigens and these are targets of damaging graft-versus-host (GVH) responses and potentially therapeutic graft-versus-leukaemia (GVL) responses following bone marrow transplantation (BMT). Knowledge of the peptide identity of HY epitopes allows monitoring of immune responses following BMT, using fluorescent tetramers, and also offers the possibility of inducing immunological tolerance.
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PMID:The case of the midwife scientist. 1141 93

We report a case of transient myeloproliferative disorder (TMD) in a neonate without features of Down syndrome (DS) with clonal karyotype evolution, after apparent spontaneous resolution of TMD, but eventually progressing to acute megakaryoblastic leukemia (AMKL). The patient had petechiae, thrombocytopenia, and blastemia. Trisomy 21 with a satellited Y chromosome (Yqs) was found in proliferating blasts. A stimulated peripheral blood culture confirmed the constitutional origin of the Yqs, but did not reveal the presence of any trisomic 21 cell. By the age of 3 months, clonal chromosome evolution in the form of an interstitial deletion of the long-arm of chromosome 13 [del(13)(q13q31)] was detected along with trisomy 21 in unstimulated bone marrow cultures. However, remission was achieved without treatment at the age of 4 months. Trisomy 21 and del(13)(q13q31) were not identified in either cytogenetics or fluorescence in situ hybridization studies at that time. The child was asymptomatic until the age of 20 months when anemia and thrombocytopenia prompted a bone marrow biopsy, revealing changes consistent with AMKL. The remission proceeded by clonal karyotype evolution in a neonate with TMD demonstrates that clonal karyotype evolution does not indicate an immediately progressive disease. However, the development of AMKL after TMD in this case illustrates the increased risk for leukemia in TMD cases, even without DS. The gradual clonal evolution of the blasts in our patient suggests that "multiple hits" oncogenesis applies to TMD progression to acute leukemia.
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PMID:Acute megakaryoblastic leukemia after transient myeloproliferative disorder with clonal karyotype evolution in a phenotypically normal neonate. 1190 41

A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnormalities of chromosome 13, deletion of Y chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS, aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended on the specific abnormal cytogenetic pattern. Most deaths related to leukemic transformation occurred in patients with abnormalities of chromosome 7 or complex cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen most often in refractory patients who had failed to respond to therapy. In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent. Although AA patients with monosomy 7 showed a similar prognosis to those with primary MDS, trisomy 8 in AA appears to have a more favorable prognosis than in MDS.
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PMID:Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. 1196 74

Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA) provides a promising way to treat leukemia relapse in allogeneic chimeras. Here we describe the in vitro generation of CTL against mHA in the dog. We tested their inhibitory effect on the growth of hemopoietic progenitor cells stimulated by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs were characterized by morphology, high expression of MHC class II and CD1a, and the absence of the monocyte-specific marker CD14. Characteristically these cells stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex vivo by coculture with DCs of DLA-identical littermates or in vivo by immunization of the responder with DCs obtained from a DLA-identical littermate. In suspension culture assays the growth of hemopoietic progenitor cells was inhibited in 53% of DLA-identical littermate combinations. In canine families mHA segregated with DLA as restriction elements. One-way reactivity against mHA was found in five littermate combinations. In two cases mHA might be Y chromosome associated, in three cases autosomally inherited alleles were detected. We conclude that CTL can be produced in vitro and in vivo against mHA on canine hemopoietic progenitor cells using bone marrow-derived DCs.
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PMID:Minor histocompatibility antigens on canine hemopoietic progenitor cells. 1279 11

Male recipients of transplants from female (F-->M) hematopoietic stem cell donors represent a special group in whom donor T cells that are specific for recipient minor histocompatibility antigens encoded by Y-chromosome genes may contribute to a graft-versus-leukemia (GVL) effect and to graft-versus-host disease (GVHD). We examined the contribution of donor/patient sex to the risk for relapse and GVHD in 3238 patients who underwent HLA-identical sibling hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies at a single institution. Compared with other sex combinations, male recipients of female transplants had the lowest risk for relapse and the greatest odds for GVHD. Remarkably, after controlling for GVHD as a time-dependent covariate, F-->M HSCT still exhibited a lower risk for relapse than other sex combinations, demonstrating a selective GVL effect distinct from that contributed by GVHD. A reduction in relapse after F-->M HSCT was observed in patients with chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL). Taken together, these data suggest that minor H antigens encoded or regulated by genes on the Y chromosome contribute to a selective GVL effect against myeloid and lymphoid leukemias after F-->M HSCT.
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PMID:Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. 1296 70


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