CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease

Abstract

Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV H ) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV H mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3% Damle et al 2 suggested that the expression of surface CD38 on the tumor cells gave the same information and might be a surrogate assay. Initial analysis of 50 of our patients, however, failed to show a significant correlation between IgV H gene mutation status and CD38 expression. 5 CD38 is a type 2 trans-membrane glycoprotein that acts as a complex ecto-enzyme with adenosine diphosphate-ribosyl cyclase and cyclic adenosine diphosphate-ribose hydrolase activities. 6 In the B-cell compartment CD38 is not a lineage marker, but it is expressed at times during B-cell development when cell-to-cell interactions are crucial to development. 7 Examples include an early bone marrow precursor cell, cells in the germinal center, and plasma cells. 8 All the factors that signal its up-regulation are as yet unknown, but they include ␣-and ␥-interferon. 9 Standard management for stage A B-CLL is to delay therapy until there is evidence of progression. 10 Meta-analysis of 6 trials involving 2048 patients showed no benefit of immediate treatment over delayed treatment with alkylating agents. 11 Nevertheless, approximately half the patients allocated to the watch-and-wait option eventually require treatment, and one fourth die of a cause related to B-CLL. 12 If those whose disease is destined to progress are identifiable at diagnosis, either by knowledge of the degree of CD38 expression or the status of IgV H mutations, it might be feasible to treat the disease more effectively with newer agents while the tumor burden is low.We have detailed clinical information on more than 600 patients with B-CLL who have been treated and followed up by this department for the past 28 years. This long follow-up has enabled us to appreciate fully the natural history of B-CLL and has allowed us to take death, rather than simply time to progression, as the end-point for our studies. For the past 10 years we have been cryopreserving sequential blood samples from many of these patients. This has given us a rare opportunity to examine IgV H mutations and CD38 expression as prognostic indicators for B-CLL. Moreover, we have the opportunity to establish whether CD38 expression is a reproducible and stable marker in the disease. Patients, materials, and methodsOne hundred forty-five patients were chosen from more than 600 patients with B-CLL who have attended the hematology clinics of the Royal For personal use only. on May 11, 2018. by guest www.bloodjournal.org From Bournemouth Hospital in the past 28 years. An attempt was made to include a representative ...

High expression of Bfl‐1 contributes to the apoptosis resistant phenotype in B‐cell chronic lymphocytic leukemia

“…Hence there is no reason that our defined groups would correlate with the presence or absence of IgV mutations. Furthermore, there was no significant difference between the groups in the mean expression of CD38, which has been suggested as a surrogate marker for IgV mutation status 5 or at least as a predictive factor 45 ). However, the proportion of positive cases (cut-off 30%) was higher in the rB-CLL group (4/7 vs. 2/7, Table I).…”

Igβ(CD79b) mRNA expression in chronic lymphocytic leukaemia cells correlates with immunoglobulin heavy chain gene mutational status but does not serve as an independent predictor of clinical severity

“…These include determinations of CD38 surface expression [21,[44][45][46], chromosomal abnormalities [24,47,48], telomere length [49], and thymidine kinase expression [50][51][52]. The utility of certain biological markers, e.g., CD38 [23,24,44] and chromosomal abnormalities [46,48] may be unreliable and/or compromised by instability during the course of the disease. Therefore, there is a need for additional reliable and simple prognostic tools.…”

“…We next assessed the relationship between Igb mRNA expression and ZAP70 expression, another reported parameter of CLL severity and prognosis [21][22][23][24][25][26][27][28]. An immunohistochemical assay of ZAP70 protein expression in peripheral lymphocytes was developed for this purpose.…”

“…The Igb mRNA expression levels in the CLL cells were compared to two recently identified benchmark parameters of CLL severity, somatic hypermutation (SHM) status of the immunoglobulin variable heavy chain (IgV H ) gene and ZAP70 protein expression [21][22][23][24][25][26][27][28]. We report a significant correlation between Igb mRNA levels and the SHM status in CLL.…”

Autoimmune haemolytic anaemia emerging during Campath treatment in a patient with CD5 negative chronic lymphocytic leukaemia

“…Moreover, CD38 expression had increased on out patient's lymphoid cells after Campath treatment. One study noted that CD38 expression increased after treatment on residual cells in few patients variably treated with chlorambucil, epirubicin and fludarabine [11]. This leads to the possibility of autoimmune clones emerging within the CD38 positive population.…”