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Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group

Journal of Cancer Therapy 2019年第6期10卷 442-457页

作者： mona hilmy alrayes Reham Hammad Mohamed Abd Alazim Hussein EL Baddiny Maha Saleh Madbouly Ibrahim Mahmoud Hammad Clinical Pathology Department Faculty of Medicine (for Girls) Al-Azhar University Cairo Egypt Clinical Pathology Department National Cancer Institute Cairo University Cairo Egypt Department of Pediatric Oncology National Cancer Institute Cairo University and Children’s Cancer Hospital Egypt Cairo Egypt

Angiogenesis has an important role in pathophysiology of cancer. FMS-like tyrosine kinase 3 (FLT3) is implicated in hematopoietic malignancies. Their role in childhood acute lymphoblastic leukemia (ALL) pathogenesis needs more enlightenment. Expression of vascular endothelial growth factor receptor-1 and -2 (VEGFR-1 and -2), as well as FLT3 were assessed by flow cytometry in bone marrow (BM) blasts of 55 newly diagnosed children with ALL. Patients included B cell ALL (B-ALL) group (n = 41) and T cell ALL (T-ALL) group (n = 14). Comparison between groups revealed a significant increase in blasts percent (%) expressing FLT3 and FLT3 intensity detected in B-ALL group (p = 0.004 and p = 0.02, respectively). In B-ALL patients, a significant positive correlation was seen between blasts % expressing FLT3 and blasts percentage infiltrating BM (r = 0.405;p = 0.009), also positive correlation was seen between % of blasts expressing VEGFR-1 and VEGFR-2 (r = 0.704;p 0.001). In T-ALL group, blast % expressing FLT3 revealed significant positive correlations with blast % expressing VEGFR-1, and those expressing VEGFR-2 (r = 0.627;p = 0.016, and r = 0.654;p = 0.011, respectively). In addition, significant correlation was seen in blasts % expressing all;FLT3, VEGFR-1 and -2, with blasts % expressing stem cell marker CD34 (r = 0.826;p = 0.001, r = 0.596;p = 0.041, and r = 0.798;p = 0.002, respectively). Conclusion: Expression of VEGFR-1, VEGFR-2 and FLT3 were demonstrated and linked on leukemic blasts of ALL which highlights their role in pathogenesis. FLT3 expression plays a role in facilitating blasts proliferation in BM in B-ALL. FLT3, VEGFR-1 and -2 could be used in future profiling of CD34+ leukemic stem cell pool in T-ALL.

关键词： Childhood Leukemia Angiogenesis Vascular Endothelial Growth Factor Receptors FLT3 Acute Lymphoblastic Leukemia

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