• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • There was a statistical significant correlation


    There was a statistical significant correlation between CD39 expression on CD4+ T cells and CD38 and ZAP-70 (Table 3). Del 6q was detected in 19 patients (63.3%) with a range of 2–75% and a mean of 32.97 ± 14.85. As regards to the staging system, del 6q was significantly higher in high risk group of patients (p = .01) as shown in Table 1, also there was a significant correlation between del 6q, CD39, CD38, and ZAP-70 (Table 3). Twenty-five (83.3%) CLL patients had an indication to treatment whereas five (16.6%) patients had no indication to treatment. Regarding the course of the disease, there was a significant relation between expression of CD39 and response to treatment with one patient (8%) achieving complete remission (CR), three patients had partial remission (PR) and eight patients (66.7%) had refractory disease (RD) with (p = .04). According to presence of 6q deletion, three patients (15.7%) had CR, five patients (26.3%) had PR, and 11 patients (57.8%) had RD with p-value of .03 as shown in Table 4. With a median follow up of 36 months, median OS in patients with positive CD39 was 30 months (range, 20.7–41.9 months) with no significant difference between patients with positive and negative CD39 (p = .385) as shown in Fig. 3. Median DFS was 17.5 months in CD39 positive patients versus 15 months in CD 39 negative (p = .8) as shown in Fig. 4. There was a significant difference in OS between patients with positive and negative del6q with mean OS in patients with del 6q was 22.4 ± 22.6 months versus 46 ± 14 months in patients with negative del 6q with significant difference (p = .047) as shown in Fig. 5, however, there was no significant difference in DFS between both groups (Fig. 6).
    Discussion The main hallmark of cancer cells now is their ability to cause host immunosuppression by the activation of multiple immune check points. Blockage of these pathways using several Dexamethasone has led to durable responses and increased survival rates in cancer patients [5]. Recently, CD39/CD73-adenosine pathway has been recognized as an important immune function regulator. It plays an important role in tumor mediated immunosuppression by removing proinflammatory ATP and production of adenosine which causes inhibition of T cell proliferation [4]. In this study, CD39+ expression on CD4+ T helper cells in CLL patients was significantly higher compared with the control group. This finding supports the recent observation that CD39 is significantly higher expressed in many different types of cancer cells than in normal tissues by infiltrating lymphocytes, tumor cells, and tumor stroma [4]. Levels of CD39+ CD4+ T cells in this study were higher in advanced stage disease which is in agreement with previous studies which demonstrated a significant difference between early and late stages of the disease [6], [7]. Also, in this study, expression of CD39+ CD4+ T cells was positively correlated with CD38 and ZAP-70 expression which are well known as prognostic markers of advanced disease which supports previous results of Pulte et al. [7] but contrasted the results of Perry et al. [6] who found no correlations between them. However, in this study, there were no significant differences in overall survival or disease-free survival between patients with positive and negative CD39. The nature of gene predisposition in CLL is still unclear. Most of the reported genetic abnormalities in CLL are not constant and it is not known whether they occur as early events or during evolution of the disease. The most common abnormalities in CLL are trisomies, mutations, or deletions [8]. We examined the prognostic significance of 6q- in CLL patients. 6q- was found positive by FISH in 63.3% of patients. This is more or less in agreement with Zhang et al. [9], who found that deletions of 6q23-q24 detected in four of nine B-CLL patients. However, Stilgenbauer et al. [10] and Merup et al. [11], found that deletions involving 6q were found in 7% and 6%, respectively. The discrepancy between our results and the previous results could be explained by the lower number of patients in our study. In addition, on reviewing their study, we found that the majority of CLL patients who were included in that study had early-stage disease. By contrast, only 20% (6/30) of the patients included in our study were in the low risk group in the modified Rai staging system, with the majority (80%) in the intermediate and high-risk group, which were associated with significant positive correlation with CD39+ expression on CD4+ T cells. This agrees with Cuneo et al. [12] who found that CLL patients with del 6q were an intermediate-risk group. Also, Welson et al. [13] observed that all CLL patients (100%) with 6q deletion were allocated to Stage C and Stages III and IV of Binet and Rai staging systems, respectively. In our study, presence of 6q- was associated with significant positive correlation with Rai staging, CD39+ expression on CD4+ T cells, CD38, and ZAP-70 expression and this was translated into a statistical significant difference in OS between patients with positive 6q- and negative 6q-.