Background The proliferation of acute myeloid leukemia (AML) blast into the bone marrow microenvironment is controlled by cytokines. Interleukin-4 (IL-4) has recently been discovered to suppress the development and persistence of AML cells selectively. Intron three of the Interleukin-4 (IL-4) gene contains a 70-bp minisatellite region polymorphism that may influence gene transcriptional activity and subsequently affect the production level of IL4. We investigated the IL-4 gene intron three variable number tandem repeat (VNTR) polymorphism as a molecular marker in AML associated with clinical and laboratory variables and a prognostic factor for therapeutic response and disease outcome. Results IL-4 gene intron three minisatellite regions polymorphism was assessed in 60 adult AML patients and 60 healthy controls, comparable concerning age and gender, using polymerase chain reaction. Three study marker genotypes were detected in AML patients; P1/P1 (3%), P1/P2 (40%), and P2/P2 (56.7%). The frequency of P2 alleles was significantly more in AML patients than in healthy controls (76.7% versus 25%; P < 0.001). Compared to the heterozygous group and P1/P1 carriers, AML patients with the homozygous P2/P2 genotype had a higher total leucocytic count and increased blast percentages in bone marrow or peripheral blood, besides a lower platelet count. P2P2 genotype was also significantly associated with poor therapeutic response, higher susceptibility to disease recurrence and shorter overall survival and disease-free survival. Conclusion The IL-4 intron 3 VNTR polymorphism could be included in the molecular risk stratification of AML to predict poor disease. This information can be utilized in incorporating biological therapy into the present therapeutic protocols to enhance chemotherapy regimens’ current low response rates.

BACKGROUND Autophagy is the cellular mechanism for homeostasis maintenance and survival under stressful conditions like hypoxia and nutrient deprivation. It has been extensively studied in various types of malignancies. However, the relationship between cancer and autophagy is still controversial. Researchers have been focusing on the exploitation of autophagy in the invention of new cancer therapeutics. Acute lymphoblastic leukemia is one type of malignancies with the highest resistant rates and worst prognosis. Knowing whether autophagy has a role in its initiation or progression would be of a great benefit. It would open the door to adding autophagy modulator drugs to conventional treatments in clinical trials to improve disease outcome. AIM To assess the basal level of autophagy in newly diagnosed ALL cases using ATG5 expression level, a key autophagy gene, and detect the relationship between the level of autophagy and prognosis. PATIENTS AND METHODS 35 newly diagnosed ALL patients and 15 healthy controls were included in the study. ATG5 RNA transcript level was measured by real time RT-PCR in all subjects using peripheral blood samples. Patients were followed up monthly for a year by Bone marrow aspiration and minimal residual disease using multiparameter color flowcytometry to detect resistance and early relapse. RESULTS ATG5 expression level was significantly higher in the ALL patients compared to the control group. Cases had approximately twice the mean expression value of the control (2.15±2.2 vs 1.09 ± 0.47). (P value = 0.01). The median value of the ATG 5 expression of the cases was used as a cut point to divide them into two groups of low and high expression. More B-ALL patients were in the high ATG5 group (83% vs 53%, P value=0.05). In addition, the high ATG5 group displayed a significantly lower haemoglobin level, platelet count, LDH level and CD 8 expression than the low ATG5 group (Mean Hb level of 7.7 g/dl vs 9.6 g/dl respectively, P value=0.04, Mean Platelet count of almost 55 x 109/L vs 105 x 109/L respectively, P value = 0.01, Mean LDH level of 455 vs 1260 U/L respectively, P value=0.02, CD8 + patients 0% vs 23% respectively, P value=0.05). Although ATG5 level was also more associated with a higher white blood cell count, the presence of extramedullary disease, a positive Philadelphia chromosome and post induction refractoriness, no statistical significance was found. ATG5 expression neither showed a significant relation with patients overall survival nor their disease free survival. CONCLUSION Basal autophagy level is high in ALL disease and associated with more aggressive disease characteristics. More researches are needed to detect its clear relationship with disease prognosis.

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Background: Immune thrombocytopenia (ITP) is a disorder of antibody mediated destruction and inhibition of production of platelets. In general, this is an idiopathic disease, and it is unclear what are the immune factors related to disease predisposition, severity, and especially response to treatment. Objective: The aim of the work was to measure the level of Immunoglobulins M (IgM) and A (IgA) in patients with immune thrombocytopenic purpura (ITP) and to detect their relation to treatment response. Patients and Methods: The serum level of both IgA and IgM were measured by ELISA assay in 60 newly diagnosed ITP patients received standard treatment in the form of steroids. Patients were aged from 16 to 45 years. Results: Median level of IgA was higher in ITP patients at presentation in comparison to average normal population which was of no statistical significance while ITP patients had lower median level of IgM at presentation in comparison to average normal population with no statistically significance. No significant correlation could be detected between level of IgA and IgM and platelets count in ITP patients after one month and 3 months of treatment. This study indicated that non responder patients had IgA level higher than that of responder patients but of no statistically significant difference. (P value=0.536). Conclusion:It could be concluded that statistically significant difference between responder and non-responder ITP patients as regard the level of IgM denotes that patients who had IgM level below the median were more resistant to steroids which is the standard treatment in ITP.

Conclusion:The management of thrombotic events in APL is a challenge, since the increased bleeding risk associated with anticoagulation must be weighed against the potential lethality of the thrombosis if it is left untreated. Central nervous system arterial thrombosis has a particularly poor prognosis. We present a case that illustrates the importance of early APL treatment with ATRA and supportive measures in reverting the coagulopathy of the disease.

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