HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance

Shah, Nina; Decker, William K.; LaPushin, Ruth; Xing, Dongxia; Robinson, Simon N.; Yang, Hwai‐I; Parmar, Simrit; Tung, S.; O’Brien, Susan; Fernandez-Vina, M.; Shpall, Elizabeth J.; Wierda, William G.

doi:10.1038/leu.2011.30

Cited by 29 publications

(20 citation statements)

References 11 publications

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“…Previous reports have suggested that homozygosity of HLA is associated with the development of CLL 41,42 and DLCBL, 43 which we also report for all HLA class I loci. Although consanguinity among cases cannot be formally assessed, it would not account for the magnitude of this observed risk (OR 5 1.16-1.19).…”

Section: Discussionsupporting

confidence: 56%

“…However, a recent CLL association result from MD Anderson indicated that the A1;C7;B8 haplotype was predisposing for CLL. 41 We note the MD Anderson dataset included only patients that proceeded to allogeneic transplant, which likely biases cases toward more common HLA alleles, whereas the NMDP dataset included patients that did not identify a matched donor and/or did not proceed to transplant.…”

Section: Discussionmentioning

confidence: 99%

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Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations

Gragert

Fingerson

Albrecht

et al. 2014

Blood

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations

Gragert

Fingerson

Albrecht

et al. 2014

Blood

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“…A bias in HLA usage, mainly concerning the development of severe disease, was reported in CLL. [26][27][28] In addition, a very recent study associated HLA specificities with prognosis in MBL, 29 pointing to the existence of protective HLA-restricted T cell interactions involved in the control of tumor expansion. In line with this, two of our MBL cases with a shared TR CDR3 region also shared five of the eight analyzed HLA loci.…”

Section: Discussionmentioning

confidence: 99%

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL

et al. 2018

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Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 and CD8 T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

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“…HLA homozygosity could provide a selective advantage to neoplastic cells by restricting the potential of presentation of tumor-specific epitopes by HLA antigens. Interestingly, a recent study 19 has reported a slightly increased homozygosity rate at HLA-A, B, C, DRB1 loci in a large cohort of chronic lymphocytic leukemia patients compared with HLA allele distribution in the population. Copy-neutral LOH at 6p arms has recently been observed in 13% aplastic anemia patients, all involving the HLA region.…”

Section: Discussionmentioning

confidence: 97%

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

Dubois¹,

Sloan‐Béna

Cesbron

et al. 2012

Leukemia

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Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3 --4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with o80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.

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HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance

Cited by 29 publications

References 11 publications

Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations

Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

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