Quantification improves the prognostic value of CD38 expression in B‐cell chronic lymphocytic leukaemia

Mainou‐Fowler, Tryfonia; Dignum, Helen; Taylor, Pennie; Dickinson, Anne; Saunders, Peter; Proctor, Stephen J.; Summerfield, Geoffrey

doi:10.1046/j.1365-2141.2002.03673.x

Cited by 34 publications

(22 citation statements)

References 24 publications

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“…Among the HLA-B alleles, HLA-B52:01 allele was expressed at a higher frequency in CLL patients expressing CD38 molecule, compared to CD38 -patients (OR=4.77, p=0.037). Association between expression of CD38 and/or lack of IGHV mutation with disease progression has been reported in various studies [7,43,44]. Accordingly, HLA-A32:01, A33:01 and B52:01 alleles seem to be positively associated to disease progression in our CLL patients.…”

Section: Discussionsupporting

confidence: 65%

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

et al. 2014

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Chronic lymphocytic leukemia (CLL) is a malignant disorder of B cell origin, with low incidence in Asian populations. In this study we investigated the HLA-class I A and B allele frequencies in 87 Iranian CLL patients and 64 healthy controls using sequence specific primer-polymerase chain reaction (SSP-PCR) technique. Our results showed increased frequencies of HLA-A11:01 (p=0.02) and HLA-B35:01 (p=0.002) alleles and HLA-A11:01/B35:01 haplotype (p=0.036) and decreased frequencies of HLA-A01:01 (p=0.02), HLA-A26:01 (p=0.03), HLA-B65:01 (p=0.03) and HLA-B53:01 (p<0.00001) alleles in CLL patients compared to the control group.Classification of the patients into non-progressive and progressive groups did not reveal significant differences for the frequency of any of the HLA-A and B alleles or haplotypes between these two subtypes. Comparison between patients with immunoglobulin heavy chain variable region genes (IGHV) mutated (n=56) and unmutated (n=31) subtypes showed a significant increase in HLA-A32:01 (p=0.05) and HLA-A33:01 (p=0.05) alleles in IGHV unmutated patients compared to IGHV mutated patients. Similarly, a higher frequency of HLA-B52:01 (p=0.037) alleles was observed in CD38+ compared with CD38-patients. Our results obtained from an Iranian population indicate that CLL is associated with distinct HLA class I alleles and haplotypes some of which are linked to disease prognostic factors.3

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Section: Discussionsupporting

confidence: 65%

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

et al. 2014

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“…This quantification can be achieved by measuring CD38 ABC (antibodies bound per cell). The first study on CD38 ABC of leukemic cells in CLL patients was published in 2002 by Mainou-Fowler et al (8). A significant shorter time to first treatment and a shorter disease-specific survival was seen in patients with more than 250 ABC as compared to those with less than 250 ABC.…”

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confidence: 99%

CD38 as a prognostic factor in B cell chronic lymphocytic leukaemia (B‐CLL): Comparison of three approaches to analyze its expression

Boonstra¹,

Lom²,

Langerak³

et al. 2006

Cytometry Part B Clinical

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Background: Increased CD38 expression by leukemic cells has been suggested as an adverse prognostic factor in B-CLL. Several approaches have been proposed to quantify its level of expression by flow cytometry.Methods: We compared the use of (i) the percentage of CD38 positive cells, (ii) CD38 antibodies bound per cell (ABC), and (iii) a semi-quantitative method based on the shape of the CD38 histogram, within a cohort of 78 B-CLL patients.Results: A decreased overall survival was seen with >30% CD38 positivity among B-CLL cells, with CD38 ABC >100, and with bimodal or unimodal, strongly positive CD38 histograms. However, patients with unimodal weakly positive CD38 histograms also showed a significantly reduced survival as did patients with intermediate proportions (i.e. 5-30%) of CD38+ cells. Furthermore, within the group with <5% CD38 positivity among their B-CLL cells, 84% of patients showed prognostically favourable mutated IGVH gene segments and 100% had low ZAP70 gene expression. For 5-30% CD38 positivity, these proportions were 50 and 83%, while for >30% CD38 positivity, these proportion were only 28 and 56%, respectively.Conclusions: We found a simple method of quantitation of CD38 expression (i.e., >5% CD38 positivity among B-CLL cells) to be sufficient to identify patients with an unfavourable prognosis. The level of CD38 expression as defined with this method correlated well with the IGVH mutation status and ZAP70 gene expression. q

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“…CD38 expression was also initially reported by Damle et al. to be correlated with IgV H mutations [1], however subsequent studies showed only some degree of correlation [6,7]. Irrespective of the extent of concordance with rearrangement of the IgV H genes, CD38 expression was proved by many investigators to be a reliable predictor of the outcome in B-CLL [8,9].…”

Section: Introductionmentioning

confidence: 95%

ZAP-70 and CD38 expression are independent prognostic factors in patients with B-cell chronic lymphocytic leukaemia and combined analysis improves their predictive value.

Hus

Bojarska‐Junak²,

Dmoszyńska³

et al. 2008

Folia Histochem Cytobiol.

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Abstract:Recently identified biological risk factors in B-cell chronic lymphocytic leukemia (B-CLL) include ZAP-70 and CD38 expression. The present study was conducted to clarify whether a combined analysis could improve predictive impact of these two parameters. We examined the expression of ZAP-70 and CD38 by flow cytometry method in 217 newly diagnosed, consecutive, unselected and well characterized B-CLL patients in relation to laboratory parameters and clinical outcome. We confirmed that both ZAP-70 as well as CD38 were independent of prognostic factors. There was a significant correlation between the percentage of leukemic cells positive for ZAP-70 and the percentage of CD38+CD19+ cells (R=0.629; p=0.000001). Combined analysis of ZAP-70 and CD38 showed concordant results in 158/217 patients (72.8%), while in 59 patients the results were discordant (27.2%). A mean treatment free survival (TFS) was the longest in ZAP-70-CD38-patients (45.6 months, comparing to 13.6 months in ZAP-70+CD38+ group). Also a mean overall survival was the longest in ZAP-70-CD38-patients (224.7 months compared to 77.9 months in ZAP-70+CD38+ patients).

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Quantification improves the prognostic value of CD38 expression in B‐cell chronic lymphocytic leukaemia

Cited by 34 publications

References 24 publications

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

CD38 as a prognostic factor in B cell chronic lymphocytic leukaemia (B‐CLL): Comparison of three approaches to analyze its expression

ZAP-70 and CD38 expression are independent prognostic factors in patients with B-cell chronic lymphocytic leukaemia and combined analysis improves their predictive value.

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