Correlation Study on HLA-DR and CD117 (c-Kit) Expressions: Its Prognosis and Treatment Response in Acute Myeloid Leukemia Patients

Abstract

Introduction: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. HLA-DR and CD117 (c-Kit) are important diagnostic markers of AML. Our objective is to determine the prognostic significance of HLA-DR and CD117 expressions in newly diagnosed AML patients and determine the correlation between HLA-DR and CD117 expressions and other prognostic markers such as cytogenetic abnormalities, FLT3-ITD, response to treatment, and patient's survival. Methods: This study included 100 newly diagnosed AML patients. All patients were subjected to clinical, morphological, cytochemical, cytogenetic analysis, molecular genetic analysis to detect FLT3-ITD, and Flowcytometric detection of HLA-DR, CD117, and CD 34. Results: The results showed that HLA-DR expression was found in 75 patients (77.3%), while CD117 expression was found in 63 patients (64.9%). Patients with HLA-DR expression showed significantly higher mean Hb concentration, significantly higher platelet count, associated with AML-FAB subtypes (M0, M1, and M2), CD34 expression, and favorable cytogenetic group. M3 subtype was significantly associated with HLA-DR-ve. While patients with CD117 expression showed significantly lower platelets count. Double positive patients (HLA-DR+ve/CD117+ve) showed significant association with the intermediate cytogenetic group, while double-negative patients (HLA-DR-ve/CD117-ve) were associated with the favorable and intermediate cytogenetic group and either positive (HLA-DR+ve /CD117-ve or HLA-DR-ve/CD117+ve) associated with poor cytogenetic groups. FLT3-ITD expression had significantly worse overall survival. Conclusion:The current study suggested that the expression of CD117 and HLA-DR may be a prognostic marker in AML, as they are associated with M0, M1, and M2 FAB subtypes; moreover, patients with combined HLA-DR and CD117 positive expression are associated with CD34 expression and intermediate cytogenetic group.

A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia

“…Following lysis of red blood cells by RBC lysis buffer according to manufacturer’s protocol (Biolegend, 420301), the blood was washed twice by Cell Staining Buffer (Biolegend, 420201), then stained with anti-human HLA-DR (BD, 560744). Human HLA-DR positivity (>1% in PB) was used to confirm Kasumi-1 and FA-AML1 engraftment [ 19 ]. Engraftment of hPBMCs was determined by flow cytometric analysis.…”

Targets for chimeric antigen receptor T-cell therapy of acute myeloid leukemia

“…Enhancement of c-kit can occur in granulocyte, melanocytes, inhibitory neurons, and monocytes. C-kit expression has been reported between 64% to 100% of AML patients with median bulk AML expression of 70% ( 64 , 65 ). The generation and validation of anti-c-kit CAR T-cells in vitro and in vivo models show both CAR T-cell directed killing against AML cells and primary HPCs ( 65 ).…”

Impact of HOXB4 and PRDM16 Gene Expressions on Prognosis and Treatment Response in Acute Myeloid Leukemia Patients

“…Early detection of FLT3-ITD may allow for more sustained and permanent remissions. 24 Additionally, previous articles revealed that mutations in Nucleophosmin 1 ( NPM1 ) exon 12 may have prognostic importance in Egyptian AML patients, providing vital new prognostic information and potentially significantly affecting therapy choices. 25 , 26 …”

“…Early detection of FLT3-ITD may allow for more sustained and permanent remissions. 24 Additionally, previous articles revealed that mutations in Nucleophosmin 1 (NPM1) exon 12 may have prognostic importance in Egyptian AML patients, providing vital new prognostic information and potentially significantly affecting therapy choices. 25,26 The current study evaluated the potential prognostic and predictive roles of HOXB4 and PRDM16 in newly diagnosed AML patients and established a correlation between their expression and other prognostic factors such as cytogenetic abnormalities, FLT3-ITD, NPM1 exon 12 mutations, response to treatment, and patient survival.…”