Author(s)

Mona Hilmy Alrayes^1*, Reham Hammad^1*, Mohamed Abd Alazim Hussein EL Baddiny², Maha Saleh Madbouly Ibrahim², Mahmoud Hammad³

¹Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
²Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
³Department 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.

Childhood Leukemia, Angiogenesis, Vascular Endothelial Growth Factor Receptors, FLT3, Acute Lymphoblastic Leukemia

Alrayes, M. , Hammad, R. , Baddiny, M. , Ibrahim, M. and Hammad, M. (2019) Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group. Journal of Cancer Therapy, 10, 442-457. doi: 10.4236/jct.2019.106037.