Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements.

Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

Programmed death ligand 1 expression in diffuse large B cell lymphoma: correlation with clinicopathological prognostic factors.

BACKGROUND: The prognostic value of the level of programmed death ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) is still debatable. This study examined the effect of the level of PD-L1 expression on the clinicopathological characteristics and prognosis of diffuse large B cell lymphoma (DLBCL). METHODS: A retrospective study was conducted on formalin-fixed paraffin-embedded tissue blocks of one hundred de novo DLBCL patients diagnosed from 2013 to 2016. PD-L1 expression was defined by a modified Combined-Positive Score (CPS) and their medical records were reviewed to collect their clinical, laboratory and radiological data, treatment, and outcome. RESULTS: The included patients were aged from 23 to 85 years and treated by rituximab- cyclophosphamide, doxorubicin, oncovin, prednisone (R-CHOP); 49% were males; 85% of the cases were presented at Ann Arbor stages III, IV; 33% of patients were seropositive for HCV and 87% of cases were presented with intermediate and high IPI. All included cases expressed PD-L1 using modified CPS. 27% of patients showed low PD-L1 expression (≥ 5% to < 50% of total tumor cellularity) while 73% of patients showed high PD-L1expression (≥ 50% of total tumor cellularity). High PD-L1 expression is statistically correlated with advanced stage (p 0.01), high IPI score (p 0.017), high incidence of stationary and progressive disease (p 0.002) and high incidence of relapse (p value 0.01). Five-year disease-free survival (DFS) was 29% for patients with high PD-L1 expression compared with 84.8% for patients with low PD-L1 expression (p 0.001). CONCLUSIONS: This study suggests that high PD-L1 expression in DLBCL is associated with aggressive clinicopathological features and a decreased response to R-CHOP. The level of PD-L1 expression could be an independent predictor of DFS of DLBCL. More research is mandatory to standardize the cutoff value and scoring methods.

Dynamic changes in the levels of sCD62L and SPARC in chronic myeloid leukaemia patients during imatinib treatment.

WHAT IS KNOWN AND OBJECTIVE: Chronic myeloid leukaemia (CML) microenvironment is responsible for resistance of leukaemic cells to tyrosine kinase inhibitor, altered adhesion, increased proliferation and leukaemic cells growth and survival through the secretion of many soluble molecules. We aimed at monitoring soluble L-selectin (sCD62L) and secreted protein acidic and rich in cysteine (SPARC) levels in chronic phase chronic myeloid leukaemia (CP-CML) patients and assessing the impact of imatinib on these parameters. METHODS: This prospective controlled clinical trial enrolled 35 subjects classified into two groups: control group included 10 healthy volunteers and CP-CML patients group included 25 newly diagnosed CP-CML patients received imatinib 400 mg once daily. sCD62L plasma levels, SPARC serum levels, breakpoint cluster region-Abelson1 (BCR-ABL1) %, complete blood count with differential, liver and kidney functions parameters were assessed at baseline and after 3 and 6 months of treatment. RESULTS AND DISCUSSION: At baseline, sCD62L and SPARC were significantly elevated in CP-CML patients (p < 0.05) compared to control group. After 3 months of treatment, sCD62L was non-significantly decreased (p > 0.05), while surprisingly SPARC was significantly increased (p < 0.05) compared to baseline. Moreover, after 6 months of treatment, sCD62L was significantly decreased (p < 0.05) and SPARC was non-significantly decreased (p > 0.05) compared to baseline. In addition, sCD62L was significantly correlated with WBCs and neutrophils counts, while SPARC was significantly correlated with lymphocytes count at baseline and after 3 and 6 months of imatinib treatment. WHAT IS NEW AND CONCLUSION: The elevated levels of sCD62L and SPARC at diagnosis in CP-CML patients could reflect their roles in CML pathogenesis and the dynamic changes in their levels during imatinib therapy might suppose additional mechanisms of action of imatinib beside inhibition of BCR-ABL. Furthermore, imatinib showed a significant impact on sCD62L and SPARC levels during treatment period.

Clinico-pathological significance of immunohistochemically marked tumor-associated macrophage in classic Hodgkin lymphoma.

BACKGROUND: Tumor-associated macrophages (TAM) are pivotal in remodeling of the tumor immune microenvironment and clinical outcome. Herein, we aim to evaluate the impact of immunohistochemical (IHC) expression of CD68 and CD163 in TAM on clinico-pathological features, patients' response to therapy and the overall survival (OS). RESULTS: This retrospective study was performed on paraffin-embedded tissue blocks of 100 classic Hodgkin Lymphoma (cHL) cases diagnosed and treated at our Institution. Immunohistochemical scores of CD68 and CD163 were statistically related to bulky disease (p value = 0.005 for both), tumor stage (p value = 0.02 for both), International Prognostic Score (IPS) (p value = 0.04 and 0.02 respectively), and the overall response rate (ORR) (p value = 0.001). Additionally, CD163 was also statistically related to gender (p value = 0.02), serum albumin level (p value = 0.03), and B symptoms (p value = 0.04). HCV seropositivity did not relate to either CD68 or CD163 score. Using univariate analysis revealed that B symptoms, bulky disease, IPS ≥ 3, and CD163 > 25% were associated with lower OS (p values = 0.003, 0.006, 0.001, and < 0.001 respectively), while after multivariate cox regression analysis, B symptoms, IPS ≥ 3, and CD163 > 25% were related to inferior OS (p values 0.02, 0.02, and 0.003). CONCLUSION: CD163 expressing TAM is a powerful predictor for OS in cHL, unlike CD68.

Thrombophilic Risk of Factor V Leiden, Prothrombin G20210A, MTHFR, and Calreticulin Mutations in Essential Thrombocythemia Egyptian Patients.

OBJECTIVES: Essential thrombocythemia (ET) is one of the myeloproliferative neoplasms characterized by a sustained elevation of platelet numbers with a tendency for thrombosis and hemorrhage. The aim of this work is to establish the relation between calreticulin, factor V Leiden, prothrombin G20210A, and MTHFR mutations in ET patients and the thrombotic risk of these patients. METHODS: This study was carried out on 120 ET patients and 40 apparently healthy individuals as a control group. RESULTS: There were increases in WBCs, PLT counts, PT, fibrinogen concentration factor V Leiden, and MTHFR mutation in ET patients as compared to the control group (P < 0.05). Also, there were increases in WBCs, PLT counts, and hematocrit value in thrombosed ET patients as compared to the nonthrombosed ones (P < 0.05). On the contrary, there was no significantly statistical difference in ET patients with JAK2 V617F positive mutation versus the JAK2 negative group (P > 0.05) and in patients with cardiovascular risk factors versus patients with noncardiovascular risk factors (P > 0.05). ET patients with factor V Leiden, prothrombin gene, and CALR mutations were more prone to thrombosis (odds ratio 5.6, 5.7 and 4.7, respectively). On the contrary, JAk2V 617F and MTHFR mutations have no effect on the thrombotic state of those patients. CONCLUSION: There is a significant increase risk of thrombosis in ET patients with CALR mutation, thrombophilic mutations, as well as factor V Leiden and prothrombin gene mutation with a risk of developing leukemic transformation.