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

Despite human leukocyte antigen (HLA) identity between donor and recipient, several patients develop acute graft-versus-host disease (aGVHD) after hematopoetic stem cell transplantation (HSCT) because of minor histocompatibility antigen (mHag) incompatibilities. The impact of multiple mHag disparities on the clinical outcome after HSCT still remains to be determined. We studied the genomic polymorphisms of HA-1, CD31, and CD49b and correlated mHag distribution with the occurrence of aGVHD after HSCT from HLA-matched sibling and unrelated donors. All 163 patients examined in our single-center study underwent HSCT for chronic myeloid leukemia in the first chronic phase. HA-1 and CD31 disparities are associated with increased aGVHD incidence in a subgroup of patients who test HLA-B44 supertype positive in univariate analysis. However, in a multivariate analysis, only increased patient age was confirmed as an independent aGVHD risk factor. Our findings indicate that the impact of mHag disparity on aGVHD development in HSCT from HLA-matched sibling and unrelated donors seems to be subordinated to classic aGVHD risk factors.
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PMID:Impact of disparity of minor histocompatibility antigens HA-1, CD31, and CD49b in hematopoietic stem cell transplantation of patients with chronic myeloid leukemia with sibling and unrelated donors. 1508 80

The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8(+) T cells in peripheral blood and molecular remission of relapsed BCR/ABL(+) chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-gamma in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.
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PMID:Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response. 1532 66

Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen-matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post-transplant function from January 1995 to December 2002. Of 20 patients, eight received non-myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post-transplant. Possible pre-HSCT and post-HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non-myeloablative conditioning therapy. We conclude that non-myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post-transplant pulmonary function changes.
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PMID:Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation. 1565 7

This study was aimed to investigate the corelation between the HLA (human leukocyte antigen) genes and susceptibility of leukeamia. 605 patients with leukeamia including 189 ALL, 184 AML and 232 CML were selected for this investigation. 900 normal umbilical cord blood samples from umbilical cord blood bank were used as control population compared to the leukemia patients. HLA-A, B, C typing was done by polymerase chain reaction with sequence-specific primers (SSP-PCR). The results showed that frequencies of HLA-A*26, A*68, B*56 in ALL patients were higher (4.46%, 2.65%, 1.17%), as compared with controls (2.31%, 0.95%, 0.22%), HLA-CW*06 in ALL patients was lower (3.64%), as compared with control (11.65%). In AML patients HLA-A*01 (9.41%), B*37 (3.60%) was higher and A*33 (3.60%), B*51 (4.73%) were lower than those in controls (3.57%, 1.75% and 7.64%, 7.93%). HLA-A*32, B*27, B*44, B*54, B*55 (2.18%, 3.96%, 5.06%, 4.63%, 2.84%) in CML patients were higher than those in control (0.84%, 2.04%, 3.07%, 2.44%, 1.29%). These results suggested that positive association may exist between certain HLA-class I genes and leukemias. These preliminary data may be useful for further study on the mechanisms of leukemia pathogenesis.
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PMID:[Association of gene HLA-class I with leukemia]. 1612 34

We report the results of unrelated cord blood transplantation (CBT) in a 12-year-old boy with Philadelphia chromosome- positive chronic myelogenous leukemia in the chronic phase and a high body weight (68.5 kg at transplantation). Only 1 of the 2 units used engrafted. This unit was not human leukocyte antigen (HLA) class II identical with the patient and had a much larger number of nucleated cells than the other unit (approximately 2.4:1). To our knowledge, this case report is the first to describe successful CBT from two unrelated donors to a cancer patient, who had the highest body weight among CBT recipients in Taiwan.
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PMID:Double-unit unrelated cord blood transplantation for chronic myelogenous leukemia. 1614 50

In chronic myeloid leukemia (CML), experimental studies using synthetic peptides identical to the bcr-abl fusion region have revealed the capability of specific peptides to bind to human leukocyte antigen (HLA) class I molecules (HLA-A2, A3, A11, B8) and class II molecules (HLA-DR1, DR2, DR3, DR4 and DR11). Individuals expressing HLA-A3, B8 or DR4 have a diminished risk for the development of CML in Caucasian populations. A statistically significant increase in the frequency of Cw3 and Cw4 antigens in Caucasians and European CML patients has been reported. However, HLA associations in CML have not been reported in India. In lieu of the allelic diversity of HLA in the Indian population, the present study assessed the possibility of an association of HLA molecules in Indian patients with CML. HLA A, B, C and DRB1 antigen associations in 180 clinically diagnosed Indian CML patients (aged 17 - 54 years) were analysed and compared with age-matched (n = 100) healthy individuals from the same ethnic background. In the HLA class I antigen distribution, a significant decrease was observed in HLA-A11 (25.6% versus 39%; P = 0.027, odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.31 - 0.94) and HLA-Cw6 (7.8% versus 20%; P = 0.005, OR = 0.34, 95% CI = 0.15 - 0.74). Among the DRB1 alleles, HLA-DRB1*13 (7.8% versus 17%; P = 0.031, OR = 0.41, 95% CI = 0.18 - 0.93) was decreased in CML patients. However, the differences for HLA-A11 (P(c) = 0.351) and DRB1*13 (P(c) = 0.403) did not remain significant after the application of a correction factor for the P-value. These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population and indicate that expression of HLA-Cw6 may result in a protective effect on CML acquisition in the Indian population.
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PMID:Human leukocyte antigens in Indian patients with chronic myeloid leukemia. 1632 60

Despite recent success in the treatment of early-stage disease, blastic phase (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge. The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression. To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays. Supervised microarray data analysis revealed 114 differentially expressed genes (P<10(-4)), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were downregulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-time-polymerase chain reaction and flow cytometry. Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy.
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PMID:Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. 1661 18

Natural killer (NK) cells were identified 30 years ago based on their ability to "spontaneously" kill tumor cells. The basis for NK cell recognition and activation is due to a variety of receptors that bind to specific ligands on tumor cells and normal cells. Some of these receptors have the ability to inhibit NK cell function, and other receptors activate NK cell function. Therapeutic strategies for cancer therapy are being developed based on preventing NK cell inhibition or using NK cell receptors to activate NK cells or T cells. There are intriguing clinical data from studies of bone marrow transplantation that support the idea that preventing NK cell inhibition by human leukocyte antigen (HLA) class I molecules can be a means to promote graft-versus-leukemia (GvL) effects and limit graft-versus-host disease (GvHD) in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Experimental findings also support the blockade of NK cell inhibitory receptors as a way to protect against leukemia relapse. It may be possible to use our knowledge of NK cell activating receptors and their ligands to immunize patients with modified tumor cells to promote beneficial NK cell responses and development of host antitumor cytotoxic T lymphocytes (CTLs). Finally, new data support the idea of using modified NK cell receptors as a means to target patients' T cells against their own tumor cells and induce long-term immunity against them. Tumors are essentially tissues that have overcome normal regulation mechanisms, and therefore the ability to distinguish normal cells from abnormal cells is a key part of selectively attacking tumor cells. NK cells have various receptor systems designed to recognize infected and abnormal cells. Understanding NK cell receptors and their recognition mechanisms provides new tools for the development of immunotherapies against cancer.
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PMID:NK cell receptors as tools in cancer immunotherapy. 1686 Jun 60

Cell dose is a critical determinant of outcomes in unrelated cord blood (CB) transplantation. We investigated a strategy in which CB units should contain at least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second unit had to be added. We report the results of a study that was prematurely closed owing to toxicity. Patients with advanced hematologic malignancies without a human leukocyte antigen-matched sibling or unrelated donor were eligible. Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three patients received double CB transplants. The 100-day and 1-year treatment-related mortality rates were 40 and 53%, respectively. Median time to neutrophil and platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One patient had secondary graft failure and five patients failed to engraft. Two patients are alive and disease free; 4-year actuarial survival is 33 versus 0% for patients transplanted in remission versus in relapse. We concluded that disease status was the main determinant of treatment failure in this study.
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PMID:Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignancies. 1689 72

Polymyositis may occur along with other manifestations of chronic graft vs host disease after allogeneic bone marrow transplantation (BMT). Donor lymphocyte infusion (DLI) could produce durable remissions in relapsed patients with chronic myelogenous leukemia (CML) but it may contribute to the development of polymyositis. We report in this study a 25-year-old man who suffered from a relapse of CML 4 years after a sibling human leukocyte antigen-matched allogenic BMT. The patient developed polymyositis 18 months after DLI. Mini-pulse therapy with methylprednisolone was effective for his proximal weakness and elevated creatine phosphokinase. There was no relapse of symptoms of polymyositis on tapering of the medication.
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PMID:Polymyositis complicating donor lymphocyte infusion after stem cell transplantation for relapsed chronic myeloid leukemia: report of a case and review of literature. 1693 70


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