Neemat Kassem

BACKGROUND: Multiple myeloma (MM) is a human B cell neoplasia characterized by the clonal proliferation of malignant plasma cells in the bone marrow. Worldwide, hepatitis C virus (HCV) infection is a public health problem. For MM patients, the clinical impact of preexisting HCV infection is still unclear. We aim to assess the clinical characteristics and the prevalence of the HCV infection in Egyptian MM patients. This observational study included 81 MM patients. HCV antibody assay was performed, and positive cases were confirmed using a reverse transcription-quantitative PCR (RT-PCR) method.

RESULTS: Fifteen (18.5%) patients were anti-HCV antibody positive. Only 6/15 (7.4%) patients were HCV RNA positive by RT-PCR. Liver affection in the form of hyperbilirubinemia with grade 4 adverse events was significantly higher in the anti-HCV positive/HCV RNA positive group versus anti HCV negative group (16.7% vs. 1.5%, p value = 0.005). The median HCV-RNA before the initiation of chemotherapy was 2.5 log IU/ml with mean ± SD = 4.25 ± 1.6 with no HCV reactivation. In the univariate and multivariate analysis, HCV infection was not an independent factor related to DFS. Low hemoglobin level < 10 g/dL (HR 0.59, 95% CI, 0.36-0.97, p value = 0.037) and abnormal serum total bilirubin level (HR 1.9, 95% CI 1.03-3.5, p value = 0.039) influenced DFS in the univariate analysis. However, in the multivariate analysis, serum calcium level greater than 12 mg/dL (HR 7.04, 95% CI 1.12-44.45, p value = 0.038) and abnormal serum total bilirubin level (HR 10.9, 95% CI 2.92-41.02, p value = < 0.001) remained statistically significant worse prognostic factors.

CONCLUSION: In conclusion, our study revealed the prevalence of HCV infection in Egyptian MM patients. Serologic tests at diagnosis are necessary to identify these patients, and confirmation of positive cases by molecular techniques should be mandatory, with regular follow-up for liver dysfunction. Finally, further larger studies explaining the molecular mechanisms linking HCV and the MM pathogenesis are warranted.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by clonal expansion of myeloid precursors with diminished capacity for differentiation. It develops as the consequence of a series of genetic changes in a hematopoietic precursor cell. Purpose This study aimed to investigate the correlation between GM-CSF gene expression and different molecular prognostic markers such as FLT3-ITD, NPM1 mutation A and CEBPA gene expression in 100 Egyptian AML patients. As well as, correlation with the response to induction therapy, DFS andOS in these patients.

METHODOLOGY: Quantitative assessment of GM-CSF gene expression was performed by qRT-PCR. Additional prognostic molecular markers were determined as FLT3-ITD and NPM1 mutation A together with quantitative assessment of CEBPA gene expression by qRT-PCR.

RESULTS: Patients with high GM-CSF expression levels had better OS and DFS with p value 0.004 and 0.02, respectively. However, no statistically significant difference between low andhigh GM-CSF gene expression was found regarding the response to therapy (p value= 0.08). Most patients with low CEBPA expression had resistant disease together with poor OS and DFS (P value =.

Background: Acute Myeloid Leukemia (AML) is a heterogeneous disorder with variable genetic abnormalities and
cytogenetic alterations which provide a significant disease prognosis and determine response to therapy. Purpose: We
aim to investigate the expression of the MDR1 gene in 100 Egyptian AML patients, to identify their role on both the
progression and chemotherapeutic refractoriness together with assessment of known prognostic molecular markers;
FLT3-ITD and NPM1 mutations. Methodology: Quantitative assessment of MDR1 gene expression was performed
by quantitative RT-PCR. Additional prognostic molecular markers were determined as internal tandem duplications of
the FLT 3 gene and nucleophosmin gene mutation A. Results: MDR1 gene expression levels and FLT3/ITD mutations
were significantly higher in AML patients with resistant disease with P value <0.001 and 0.002 respectively. However,
NPM1 was insignificantly higher in patients with CR P-value 0.14. In MDR positive group, wild FLT3/ITD with or
without NPM1 mutation was favorable in achieving CR with p value 0.02. MDR negative group, wild FLT3/ITD with
or without NPM1 mutation showed insignificantly higher CR rates with p value (0.35). Kaplan-Meier curves revealed
statistically significant difference between MDR1-negative and MDR1-positive patients regarding their DFS and OS
between the two groups where DFS and OS were higher in MDR1-negative patients with p value 0.004 and 0.01,
respectively. Conclusion: The results obtained by the current work together with the previous researches concerning
the study of multidrug resistance genes in AML patients provide additional evidence of the role played by these genes
as predictors of chemoresistance and poor treatment outcome.

BACKGROUND: Hepatitis C virus infection (HCV) is a major health problem in Egypt. Breast cancer is the most common cancer among Egyptian women. Considering that both diseases are frequent in the Egyptian population, it is likely that many women are affected by both.

PURPOSE: To evaluate patient safety and applicability of chemotherapy in chronic hepatitis C virus-infected patients with breast cancer.

SUBJECTS AND METHODS: We performed retrospective survey of 58 Egyptian patients diagnosed with both diseases. We retrospectively investigated the baseline patient and tumor characteristics, the toxicities of chemotherapy, and the changes in HCV viral load before and after chemotherapy, in addition to treatment received for HCV infection.

RESULTS: Forty-four (75.9%) out of the 58 patients received chemotherapy with or without trastuzumab and one patient received lapatinib. We reported 2 patients who had HCV viral reactivation. Treatment with trastuzumab or Lapatinib was not associated with elevation in liver enzymes or change in HCV RNA viral load. Treatment discontinuation occurred in 31.8% (14/44) of patients due to complications. Dose reductions and/or dose delays were common (27.2%). Elevated liver enzymes were developed in 20 out of 44 (45.5%) patients who received chemotherapy. Three patients received antiviral treatment concomitant with chemotherapy with no significant complications.

CONCLUSIONS: Greater attention should be paid to the possibility of complications including HCV reactivation, fulminant hepatitis, and interrupted chemotherapy treatments in breast cancer patients with chronic HCV infection receiving immunosuppressive drugs. Close monitoring of patients with breast cancer and HCV infection should be done.

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of
non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level.
Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate
miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology:
Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine
newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included
in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with
AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%.
miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV
41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p
value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value
=0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2.
Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate
numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels
could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic
resistance associated with higher expression levels in non-responsive patients.

PURPOSE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects.

PATIENTS AND METHODS: Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay.

RESULTS: There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti-GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy.

CONCLUSION: Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.