Kamel, A. M., N. M. El Sharkawy, E. Z. Kandeel, M. Hanafi, M. Samra, and R. A. Osman, "Leukemia Stem Cell Frequency at Diagnosis Correlates With Measurable/Minimal Residual Disease and Impacts Survival in Adult Acute Myeloid Leukemia.", Frontiers in oncology, vol. 12, pp. 867684, 2022. Abstract

Acute myeloid leukemia (AML) is a heterogenous disease in which the initiation and maintenance of the malignant clone is blamed on a rare population of leukemia stem cells (LSCs). The persistence of such a malignant population is referred to as measurable/minimal residual disease (MRD). Evaluation of MRD is the gold standard for follow-up of therapy and constitutes an independent prognostic parameter. As LSCs are the main contributor to the persistence of MRD, then MRD should correlate with the bulk of LSCs at the individual case level. MRD is measured at defined time points during therapy. However, LSCs can be evaluated at diagnosis, which ensures the advantage of early prediction of high-risk patients and allows for early therapeutic decisions. Using two simple four-color monoclonal antibody combinations (CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33) and the prism function of the Coulter Navios flow cytometer, the frequency of LSC subsets was evaluated in 84 newly diagnosed adult AML patients. For each panel, 16 possible combinations were detected. Our results showed that there was extreme variability in the percentage of the LSC fraction between different cases, as well as at the individual case level. For each LSC subset, the median value was used to divide cases into low and high expressors. LSC subsets that showed an impact on overall survival (OS) and disease-free survival (DFS) included CD123+, CD 123+/CD34-, CD34-/CD38+/CD123+, CD34+/CD38-/CD123+, CD133+, and CD133+/CD33-. On multivariate analysis, only CD123 (p ≤ 0.001, SE = 0.266, HR = 2.8, 95% CI = 1.74.7) and CD133+/CD33- (p = 0.017, SE = 0.263, HR = 1.9, 95% CI = 1.1-3.1) retained their significance for OS. Likewise, only CD34+/CD38-/CD123+ (p ≤ 0.001, HR 2.3, SE: 0.499, 95% CI: 2.4-17.4) and CD133 (p = 0.015, HR 2.3, SE 0.34, 95% CI: 1.2-4.4) retained their statistical significance for DFS. The LSC frequency at diagnosis showed a moderate to strong correlation with MRD status at day 14 and day 28. In conclusion, the level of LSCs at diagnosis correlated with MRD status at day 14 and day 28 in AML patients and had a deleterious impact on OS and DFS. It may be used as an early marker for high-risk patients allowing for early therapeutic decisions.

Kamel, A. M., N. M. El-Sharkawy, R. A. Osman, E. K. Abd El-Fattah, E. El-Noshokaty, T. A. El-Hamid, and E. Z. Kandeel, "Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.", Journal of the Egyptian National Cancer Institute, vol. 28, issue 1, pp. 31-7, 2016. Abstract

BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs.

AIM OF THE WORK: This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters.

PATIENTS AND METHODS: The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry.

RESULTS: Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=<0.01 and r=0.446, p<0.01 respectively) and CD29 with CD49c and CD49d (r=0.437, p<0.01; r=0.674, p<0.01 respectively). CD49c showed negative correlation with Rai staging (r=-0.269, p=0.033). CD11a and CD29 showed a significant relation with splenomegaly (p=0.04 and 0.03 respectively) and CD49d showed a significant relation with lymphadenopathy (p=0.02).

CONCLUSION: The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs.

Attia, H. R. M., M. Hamed Ibrahim, S. A. H. El-Aziz, N. M. Hassan, R. A. Osman, H. A. Hagag, M. E. Yassa, A. H. Abdelrahman, I. I. Salama, and M. E. Sobeih, "gene methylation status in chronic lymphocytic leukemia.", Future science OA, vol. 6, issue 7, pp. FSO583, 2020. Abstract

BACKGROUND: We aimed to investigate gene expression pattern and to explore its methylation heterogeneity in chronic lymphocytic leukemia (CLL).

PATIENTS & METHODS: Eighty one CLL patients and 75 healthy subjects were enrolled and prognostic evaluation of patients was assessed. q-realtime PCR was performed using Applied Biosystems, TaqMan gene expression assay. gene-specific CpG methylation was investigated in real time using pyrosequencing technology.

RESULTS: was differentially expressed in CLL patients. The CpG sites-1, 2 and 3 showed significantly higher mean levels than healthy controls (p = <0.001, 0.007 and 0.009). Significant association between CpG site-1 and CLL has been detected using age-adjusted logistic regression (p < 0.001).

CONCLUSION: Hypermethylation at gene CpG sites (1,2,3) is a characteristic feature in CLL.

Kandeel, E., Y. madney, R. Amin, and A. Kamel, "Role of Minimal Residual Disease in the Clinical Course of T cell Acute Lymphoblastic Leukemia in Pediatric Patients", Journal of leukemia, vol. 7, issue 1, 2019.
Osman, R. A., E. O. Rasekh, E. Z. Kandeel, T. Abdelhamid, and A. M. Kamel, "Immunophenotypic Variants of Mantle Cell Lymphoma ", Highlights of Past EHA (HOPE) Middle East & North Africa (MENA) , Egypt, 2019.
Thabet, O. E. M., W. S. Mohamed, M. Assem, A. R. A. Hamid, and R. A. Osman, "Prognostic Value of Soluble HLA-G and CD38 Expression in Patients with Chronic Lymphocytic Leukemia in Egypt", Egyptian journal of hospital medicine, vol. Volume 80, issue Issue 1, pp. Page 581-586, 2020.
Thabet, O. E. M., W. S. Mohamed, M. Assem, A. R. A. Hamid, and R. A. Osman, "Expression of Tolerogenic HLA-G Confer Worse Outcome in Patients with Chronic Lymphocytic Leukemia ", Egyptian journal of hospital medicine, vol. Volume 80, issue Issue 1, pp. Page 587-593 , 2020.
Osman, R., S. Fathy, H. A. N. A. N. SHAFIK, N. Momen, R. Kandil, and R. Zayed, "Study of epigenetic regulation of H3K27me3 in acute myeloid leukemia.", International journal of laboratory hematology, 2021.
Attia, H. R. M., M. Hamed Ibrahim, S. A. H. El-Aziz, A. H. Abdelrahman, M. E. Sobeih, H. A. A. Hagag, M. E. Yassa, R. A. Osman, R. Rawi, O. A. Y. El-Dayem, et al., "Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage.", Molecular and clinical oncology, vol. 14, issue 5, pp. 100, 2021. Abstract

The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence hybridization technique was employed to evaluate (del17p), ataxia-telangiectasia (del11q) and (del13q14) genes and the presence of trisomy 12. The serological markers β2 microglobulin (B2M) and sCD23 were measured by ELISA. The gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.

Rasekh, E. O., R. Osman, D. Ibraheem, Y. madney, E. Radwan, A. Gameel, A. Abdelhafiz, A. Kamel, and S. elfishawi, "Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients.", Annals of hematology, vol. 100, issue 3, pp. 699-707, 2021. Abstract

Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with a limited number of studies conducted to characterize its clinical spectrum and most importantly the best treatment modality. MPAL blasts show more than one phenotype either myeloid/monocytic with T- or B-lymphoid or extremely rare triple lineage associated phenotypic markers. This study aimed to characterize MPAL cases with special emphasis on comparing adult and pediatric age groups, exploring treatment regimens, and clinical outcome. Among 2571 acute leukemia patients, 102 MPAL cases fulfilling the 2008/2016 WHO diagnostic criteria of MPAL were recruited in the study. The incidence of MPAL was 4% of acute leukemia patients. Pediatric cases were 54 (53%) while adults were 48/102 (47%). Myeloid/B-lymphoid phenotype was found in 86/102 (84%), with BCR-ABL fusion gene transcript detected in 14/102(13.7%) patients. ALL-like treatment showed better response rates as compared with the myeloid based regimen (p = 0.001). MPAL behaves in a manner that resembles in clinical features, their lymphoid progenitor counterpart leukemias both in adults and pediatric patients with superior treatment response to ALL-like regimen, especially in adults.

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