CD36 as a marker of acute myeloid leukemia prognosis: A systematic review

Amantéa, Marina Chaves; Silva, Rafaela Pires da; Soares, Larissa Ranini; Pereira, João Lorenzo de Medeiros; Souza, Ana Paula Duarte de

doi:10.1016/j.htct.2025.103861

person Marina Chaves Amantéa

schoolEscola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

0000-0003-0488-5507

person Rafaela Pires da Silva

schoolEscola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

0009-0007-5089-7046

person Larissa Ranini Soares

schoolEscola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

0009-0007-1325-1086

person João Lorenzo de Medeiros Pereira

schoolEscola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

0009-0006-8299-9373

person Ana Paula Duarte de Souza ⁎

schoolEscola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

0000-0002-6021-5068

person⁎ Corresponding author. Laboratory of Clinical and Experimental Immunology, Health and Life Science School, Pontifical Catholic University of Rio Grande do Sul -
Av. Ipiranga, 6681, CEP 90619-900, Porto Alegre, RS, Brazil.
E-mail address:ana.duarte@pucrs.br (A.P.D. de Souza)

Conflicts of interest

The authors declare no conflicts of interest.

First author	Country	Study quality	n	Stem cell source	Method of CD36 quantification	Classification of AML	Results
Smith, FO²⁵	USA	Fair	176	BM	Flow cytometry	FAB	No prognostic significance for the cell surface expression of CD36 in myeloid cells.
Valet, G³¹	Germany	Fair	724	BM and PB	Flow cytometry	C + M Risk	5-year non-survivors had a higher percentage of CD36-positive AML blasts than survivors.
Perea, G³⁰	Spain	Good	266	BM	Flow cytometry	FAB and C + M Risk	The 2-year LFS rate was lower in CD36+ patients (32 %) compared to CD36− patients (56 %; p-value = 0.01). The risk of relapse was higher in CD36+ patients (63 %) than in CD36− patients (38 %). CD36+ patients with trisomy 8 had poorer LFS (0 %) compared to CD36+ patients without trisomy 8 (37 %; p-value = 0.0001). Trisomy 8 was significantly associated with CD36 expression.
El-Aziz, A²⁹	Egypt	Good	97	BM and PB	Flow cytometry, FISH	FAB	Remission was achieved in 23 of 45 (51.1 %) evaluable CD36+ patients and in 32 of 46 (69.5 %) CD36− patients. Although a higher number of responders was observed among CD36− patients compared to CD36+ patients, the difference was not statistically significant (p-value = 0.073). The 2-year OS rates were 37.5 % for CD36+ patients and 44.9 % for CD36− patients (p-value = 0.001). The 2-year LFS rates were 33.3 % for CD36+ patients and 40.6 % for CD36− patients (p-value = 0.03). CD36 expression, along with WBC count and adverse cytogenetics, were significant factors influencing OS and LFS. Multivariate analysis confirmed that CD36 expression retained its significance as an independent negative prognostic factor for both OS and LFS. CD36 expression was more commonly observed in the unfavorable cytogenetic group.
Zhang, T³³	USA	Fair	196⁎	BM and PB	Flow cytometry	FAB and C + M Risk	Using the GSE30377 dataset (n = 23), patients were dichotomized based on the median CD36 expression. Patients with high CD36 expression exhibited shorter OS, although the difference was not statistically significant (p-value = 0.114). Analysis of the TCGA dataset (n = 173) showed that when patients were dichotomized by APOC2 and/or CD36 mRNA expression Z-scores into high (Z-score ≥ 2) and low (Z-score <2) groups, those with high APOC2 and/or CD36 expression had significantly shorter OS compared to patients with low APOC2 and low CD36 expression (median OS 9.2 vs. 21.5 months, p-value = 0.017).
Chen, YJ²⁷	China	Low	70⁎	Database, undetermined (possibly tumor tissue)	RNA sequencing and immunohisto-chemistry	-	CD36 expression was significantly elevated in AML based on RNA-seq data. CD36 expression showed a strong positive correlation with infiltrating stromal scores in AML (r = 0.618, p-value <0.001). CD36 expression was positively correlated with immune scores (r = 0.609, p-value <0.001) and with the ESTIMATE score (r = 0.669, p-value <0.001), indicating a robust association between CD36 expression and the tumor immune microenvironment. CD36 expression was negatively correlated with the expression of four methyltransferases in AML
Hoch, REE²⁶	Brazil	Good	51	BM	Flow cytometry	FAB and C + M Risk	Higher frequency of CD36+ cells at diagnosis was observed in cases with disease recurrence.
Zhang, Y²⁸	China	Fair	5⁎	BM	Flow cytometry	-	CD36+ cells exhibited lower sensitivity to chemotherapeutics than CD36− cells.
Farge, T³²	France	Fair	1273	BM and PB	Flow cytometry	C + M Risk	CD36 expression in blasts at diagnosis is associated with human AML progression and relapse. CD36 was significantly associated with a worse EFS (HR: 1.55; 95 % CI: 1.17-2.05, p-value = 0.002), and a worse OS (HR: 1.69; 95 % CI: 1.18-2.41, p-value = 0.005). Median EFS of CD36-high patients was half that of CD36-low patients (252 days vs. 538 days, respectively; HR:1.65, p-value <0.0001). Median OS, which was 462 days in CD36-high patients, was not reached after 3 years in CD36-low patients (HR: 1.88, p-value <0.0001). A high CD36 protein expression at diagnosis was associated with an increased CIR after intensive chemotherapy, and a high expression of CD36 was associated with a shorter CIR (SHR: 1.53; 95 % CI: 1.07-2.19, p-value = 0.02). Intermediate and unfavorable karyotypes had a higher percentage of CD36-expressing blasts. A comparison of the genomic landscape in 224 AML did not reveal a pattern related to CD36 expression, except for FLT3 abnormalities. there's an enrichment of AML with KMT2A (11q23) or t(9;22) abnormalities in CD36-high group and an increase in t(15;17) and t(8;21) AML in CD36-low group.

[1] BM: bone marrow; PB: peripheral blood; LFS: leukemia-free survival; OS: overall survival; WBC: white blood cell; EFS: even-free survival; 95 % CI: 95 % confidence interval; CIR: cumulative incidence of relapse; FAB: French-American-British; C + M Risk: cytogenetic and molecular risk groups.

[TFN1] ^⁎
Sample size used to evaluate the outcome of interest.