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 n...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.展开更多
Despite intense research and the development of several new chemotherapeutics,the prognosis for specific subsets of acute myeloid leukemia(AML)has not improved significantly.Thus,the investigation of signaling pathway...Despite intense research and the development of several new chemotherapeutics,the prognosis for specific subsets of acute myeloid leukemia(AML)has not improved significantly.Thus,the investigation of signaling pathways associated with the pathogenesis and progression of AML has become a source for the discovery of more effective treatments.The epidermal growth factor receptor(EGFR)belongs to the HER family of tyrosine kinase(TK)receptors and is involved in the progression of a variety of solid tumors.Although the expression of members of the HER family appears to be limited to epithelial tissues and derived neoplasms,there is evidence demonstrating their role in hematopoiesis and hematological neoplasms.In AML,preclinical studies and two anecdotal cases of response to EGFR TK inhibitors(TKI)supported the EGFR signaling pathway as a potential therapeutic target.Indeed,the presence of EGFR ligands in the bone marrow microenvironment has been shown to play pathological and regenerative/protective roles in AML.However,data reporting the expression of EGFR in AML remain controversial and the EGFR pathway inhibition in AML patients has demonstrated limited clinical significance.Further studies are required to determine the relevance of the EGFR pathway in AML biology and which patients may benefit from using EGFR TKI or other drugs that target TK receptors.展开更多
文摘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.
基金supported by FAPESP grant#2013/08135-2 and FAPESP fellowship for de Almeida LY(grant No.2016/02713-2).
文摘Despite intense research and the development of several new chemotherapeutics,the prognosis for specific subsets of acute myeloid leukemia(AML)has not improved significantly.Thus,the investigation of signaling pathways associated with the pathogenesis and progression of AML has become a source for the discovery of more effective treatments.The epidermal growth factor receptor(EGFR)belongs to the HER family of tyrosine kinase(TK)receptors and is involved in the progression of a variety of solid tumors.Although the expression of members of the HER family appears to be limited to epithelial tissues and derived neoplasms,there is evidence demonstrating their role in hematopoiesis and hematological neoplasms.In AML,preclinical studies and two anecdotal cases of response to EGFR TK inhibitors(TKI)supported the EGFR signaling pathway as a potential therapeutic target.Indeed,the presence of EGFR ligands in the bone marrow microenvironment has been shown to play pathological and regenerative/protective roles in AML.However,data reporting the expression of EGFR in AML remain controversial and the EGFR pathway inhibition in AML patients has demonstrated limited clinical significance.Further studies are required to determine the relevance of the EGFR pathway in AML biology and which patients may benefit from using EGFR TKI or other drugs that target TK receptors.
