CD38 expression is a poor predictor for VH gene mutational status and prognosis in chronic lymphocytic leukemia

Thunberg, Ulf; Johnson, Anna; Roos, Göran; Thörn, Ingrid; Tobin, Gerard; Sällström, Johan; Sundström, Christer; Rosenquist, Richard

doi:10.1182/blood.v97.6.1892

Cited by 120 publications

(97 citation statements)

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“…This notion was further supported by the observation that patients with mutated V H genes had a significantly better outcome compared to patients lacking V H gene mutations (Damle et al, 1999;Hamblin et al, 1999;Maloum et al, 2000;Thunberg et al, 2001). In the present study, we were able to verify these data regarding prognosis and V H gene mutation status, since our mutated CLL cases displayed more than twice as long median survival than the unmutated cases (138 vs 55 months).…”

Section: Discussionmentioning

confidence: 91%

“…The unmutated cases are considered to originate from pregerminal centre (GC) B cells and the mutated from post-GC B cells. A more favourable prognosis has been shown for CLL cases with somatically mutated V H genes compared with unmutated cases (Hamblin et al, 1999;Damle et al, 1999;Maloum et al, 2000;Thunberg et al, 2001), indicating that CLL can be separated into at least two entities with a different clinical outcome.…”

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confidence: 99%

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Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

et al. 2003

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The immunoglobulin V H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V H genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V H gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V H gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (46%) had long telomeres (B8 kbp). Thus, both the telomere and V H gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

et al. 2003

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“…Subsequently, novel prognostic factors have been defined: lymphocyte doubling time (LDT), pattern of bone marrow infiltration, LDH, serum b2-microglobulin, soluble CD23, serum thymidine kinase, expression of CD38, cytogenetic aberrations and mutational status of immunoglobulin heavy chain variable region genes (IGV H ). [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Of these, cytogenetics and IGV H mutational status are currently the best predictors of outcome, independent of clinical stage. [13][14][15] However, their use is restricted to specialized laboratories and therefore a small number of patients.…”

Section: Introductionmentioning

confidence: 99%

High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia

et al. 2004

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Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGV H gene status (22 of 25 patients; P ¼ 0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P ¼ 0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P ¼ 0.001 for IGV H ; P ¼ 0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of V H homology (R ¼ 0.41; P ¼ 0.001). AID positivity predicted unmutated IGV H status with an odds ratio of 8.31 (P ¼ 0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P ¼ 0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.

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“…The expression of CD38 expression has been shown to be unstable over time in some patients and not in others (8)(9)(10)12,14,(29)(30)(31)(32)(33)(34) and there has been disagreement about which cutoff value to use for CD38 positivity for defining prognosis. Some investigators have used 7% (14,15,18,28), others 20% (10,13), and still others 30% (8,9,11,12,31).…”

Section: Considerations For the Measurement Of Cd38mentioning

confidence: 99%

Clinical utility of assessing ZAP‐70 and CD38 in chronic lymphocytic leukemia

Rassenti

Kipps

2006

Cytometry Part B Clinical

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CD38 expression is a poor predictor for VH gene mutational status and prognosis in chronic lymphocytic leukemia

Cited by 120 publications

References 5 publications

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications

High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia

Clinical utility of assessing ZAP‐70 and CD38 in chronic lymphocytic leukemia

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