Impact of CD34/CD309 expression in circulating endothelial progenitor cells on prognosis and response to bortezomib therapy in multiple myeloma.

Multiple myeloma (MM) is a prevalent yet incurable hematologic malignancy. Despite the proven efficacy of proteasome inhibitors in treating MM, resistance to Bortezomib-based treatments persists in a subset of patients. This case control study explores the potential of circulating endothelial progenitor cells (EPCs) as biomarkers for predicting response to Proteasome Inhibitor based therapy combined with Dexamethasone in MM patients. This study was conducted on 105 MM patients receiving bortezomib plus dexamethasone therapy and 90 healthy individuals as a control group. Utilizing 8-color multi-parameter flow cytometry, we assessed the levels of circulating EPCs, identified through CD34 FITC and CD309 PE markers at diagnosis and after one treatment cycle (4 weeks). Our findings revealed that patients exhibiting poor response to therapy showed significantly higher CD34/CD309 values than those with a good response (p < 0.001). The delineation of response based on CD34/CD309 expression was established with a cutoff ≤ 0.9 for percentage (yielding 100% sensitivity and 94.1% specificity) and ≤ 12.5 for absolute value (also with 100% sensitivity and 94.1% specificity). These results underscore the potential of EPC population levels, as quantified by CD34/CD309, to serve as a predictive biomarker for immunomodulatory treatment in MM patients undergoing Proteasome Inhibitor and Dexamethasone therapy.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients.

Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients.

OBJECTIVE: Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy. MATERIALS AND METHODS: Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45. RESULTS: Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum ß2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum ß2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response. CONCLUSION: CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.

The prognostic values of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single-center study.

Background: Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL). Materials and Methods: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test. Results: In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003). Conclusion: A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.