Frequent coexistence of RAS mutations in RUNX1‐mutated acute myeloid leukemia in Arab Asian children

Abstract

The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.

Role of RUNX1 in hematological malignancies

“…Subsequent screening of additional AML patients revealed especially high frequency of RUNX1 mutations in AML-M0, with 27% of AML-M0 patients showing inactivating RHD mutations. [123][124][125][126][127] Interestingly, biallelic RUNX1 mutations were observed in many AML-M0 patients, indicating a complete lack of RUNX1 function in their leukemic cells. 123,124 Greif and colleagues identified RUNX1 mutations in ;16% of patients with CN-AML.…”

Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia

“…Diagnostically difficult cases were reviewed by an Italian team guided by Dr. Anna Maria Testi (Department of Cellular Biotechnologies and Hematology, University “La Sapienza”, Rome, Italy) via telemedicine sessions . The diagnosis of ALL and AML was confirmed on initial unstained bone marrow (BM) aspiration smears that were transferred from Iraq and stained with May‐Grünwald‐Giemsa and myeloperoxidase at the Department of Pediatrics, Shinshu University School of Medicine . In Jordan, the diagnosis of ALL and AML was confirmed by flow cytometric analysis: CD10, CD19, CD20, CD22, and cytoplasmic CD79a were used for B‐precursor ALL; CD1a, CD2, CD3, CD4, CD5, CD7, CD8, cytoplasmic CD3, and TdT were used for T‐lineage ALL.…”

“…A total of 318 patients with ALL consisted of 264 previously reported ALL cases from five pediatric oncology centers in Iraq: the Children's Welfare Teaching Hospital in Baghdad (a major referral center for childhood cancers in the country), Central Teaching Hospital for Children in Baghdad, Basra Children's Specialty Hospital in Basra, Ibn Al‐Atheer Hospital for Children in Mosul, and Nana‐Kali Hospital for Hemato‐Oncology in Erbil, and 54 patients from KHCC in Jordan. A total of 167 patients with AML consisted of 134 previously reported Iraqi AML cases and 33 from KHCC were evaluated . All Iraqi samples and Jordanian ALL samples were collected using Flinders Technology Associates (FTA) cards between October 2009 and December 2012.…”

“…As reported previously, a few drops of diagnostic BM aspirate or PB were applied to FTA classic card matrices (Cat. No.WB120205, GE Healthcare UK Ltd., Buckinghamshire, UK) at the enrolled hospitals in Iraq and Jordan.…”

Phosphatidylinositol 3-kinase/Akt signaling as a key mediator of tumor cell responsiveness to radiation

“…Similar to solid tumors, PI3K/AKT pathways is frequently hyperactivated in hematological malignancies such as in childhood acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia, as well as in some pediatric lymphomas and lymphoproliferative disorders (22845486). This is mainly due to mutations in the upstream regulator of the pathway such as Fms-like tyrosine kinase 3 (FLT3) [155] and N-RAS [156,157] as well as overexpression of IGF-1 receptor [158] or constitutive activation of IGF-1 receptor through autocrine secretion of related ligands.…”