Utility of CD36 as a novel addition to the immunophenotypic signature of RAM‐phenotype acute myeloid leukemia and study of its clinicopathological characteristics

Abstract

Introduction: In 2016, Children Oncology Group (COG) described a new high-risk subtype of acute myeloid leukemia (AML) with a distinct immunophenotypicsignature, RAM-phenotype (RAM-AML). Data on clinical and laboratory features of RAM-AML are still limited to COG report only. Herein, we report the clinicopathological characteristics and detailed immunophenotypic features of RAM-AML patients. In COG report, 38% of RAM-AML belonged to acute megakaryoblastic leukemia (AMKL)-subtype. Hence, we further compared the immunophenotypic features RAM-AML with non-RAM-AMKL diagnosed during the same study period. Methods: We included RAM-AML and non-RAM AMKL patients diagnosed between January 2017 and December 2019. We studied their morphological, cytochemical, immunophenotyping, cytogenetic, and molecular characteristics. Mean fluorescent intensity (MFI) and expression-pattern of immunophenotypic markers of RAM-AML were compared with non-RAM AMKLs patients. Results: We identified 11 RAM-AML (1%) and 21 non-RAM AMKL (1.9%) patients in 1102 pediatric-AML patients. Seven of 11 (63.64%) patients belonged to FAB-M7subtype. CD56, CD117, and CD33 demonstrated overexpression, whereas CD45 and CD38 showed under-expression in RAM-AML patients. CD36 was consistently negative in RAM-AML, whereas moderate-bright positive in non-RAM AMKLs patients (p < 0.0001). On principle component analysis, addition of CD36 enhanced the visual-separation between RAM-AML and non-RAM AMKL clusters. Cytogenetic and molecular studies did not show any recurrent abnormality; however, RNAsequencing study revealed CBFA2T3-GLIS2-fusion in three of seven (42.8%) RAM-AML patients. Conclusion: We report the clinicopathological characteristics and the detailed immunophenotypic profile in the world's second series of RAM-AML patients. We further report a novel finding of CD36-negative expression as an additional parameter to the multidimensional immunophenotypic signature of this entity.

CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption

“…CD36 is expressed in many cell types, which mediates immune recognition, in ammation, molecular adhesion, apoptosis and lipid uptake as a scavenger receptor [25][26][27].It has been demonstrated that CD36 could regulate the proliferation, metastasis, and angiogenesis of different tumor types, such as Esophageal squamous cell carcinoma [28], gastric cancer [29], and leukemia [30]. The role of CD36 in HCC is usually related to the tumor microenvironment, and the procedure is to participate in the progression of HCC mediated by tumor metabolic reprogramming [31,32].…”

Acute myeloid leukemia with RAM immunophenotype: A new underdiagnosed entity

“…It is characterized by a unique immunophenotype of bright expression of CD56, dim to negative CD45, dim to negative CD38, and the absence of HLA‐DR 1 . There is a high frequency of acute megakaryoblastic leukemia (AMKL) among the RAM phenotype 1,2,5,9,10 . A high prevalence of more than 60% of the CBFA2T3‐GLIS2 fusion gene, which may act as pathogenic driver in this group of patients, is also reported in the literature 1,2,5,10–15 .…”

“…There is a high frequency of acute megakaryoblastic leukemia (AMKL) among the RAM phenotype 1,2,5,9,10 . A high prevalence of more than 60% of the CBFA2T3‐GLIS2 fusion gene, which may act as pathogenic driver in this group of patients, is also reported in the literature 1,2,5,10–15 . This phenotype is associated with a significantly worse outcome with a high induction failure rate and poor event free and overall survival 1,2,5,10,11 .…”

“…Acute myeloid leukemia (AML) is an extremely heterogeneous group of disorder with varied clinical, morphological, phenotypic, and genetic profiles and can involve single or multiple myeloid lineages. AML is the second most common leukemia in children, accounting for 15%–20% of all pediatric leukemias 1–4 . The peak incidence rate occurs in the first year of life, decreases up to 4 years and remains relatively constant in childhood and early adulthood 1,3 .…”

Another Abundance of Riches and more Issue Highlights!!

“…This subtype of AML was immunophenotypically characterized with bright CD56, reduced expression of CD45 and CD38 and the absence of HLA‐DR expression. In this issue Panda et al, 2021 report on studying 1102 patients with a median age of 2 years, of which 11 were RAM‐AML patients. Additionally, CD36 expression was found to be consistently absent from the immunophenotypic signature.…”