Higher prevalence of acute erythroid leukemia in high-altitude dwellers (4000 m)

Abstract

Introduction: Acute erythroid leukemia (AEL) is a rare and aggressive subtype of acute myeloid leukemia (2 %) associated with biallelic TP53 mutations. Diagnosis median age stands 67 years old with a 2.4:1 male-to-female proportion. To this, hypoxia and the hypoxia-inducible factors (HIFs) seem to play a role in AEL development through mechanisms involving erythroid differentiation, hemoglobin production, erythropoiesis regulation as well as bone marrow microenvironment modification. Thus, to discern the influence of hypoxia regarding this leukemia subtype, we searched for the prevalence of AEL and its features in the Andean population living at high altitude (4000 m). Material and Methods. Retrospective study that considered cases of AML (n=211) diagnosed in Bolivia from the period of May 2019 to October 2024, of which AEL cases (n=15) were identified and demographics, hematologic, bone marrow morphology, and immunophenotypic features were gathered. AML cases and subsequently AEL cases were categorized and statistically analyzed according to the altitude of presentation: 4000m, 2000m, and 400m. Results. AEL in Bolivia corresponded to 7.5 % of all AML cases, median age was 53 years, and predominant in male (1.5:1). At different altitudes, AEL cases at 4000 m (n=10) accounted for 14.1%, significantly higher (p=0.01) when compared to cases at 2000 m (n=3) 4.5 % and cases at 400 m (n=2) 2.7 %. AEL hematological indices did not differ among altitude groups, mean of Hb 7.3 g/dl, WBC: 10266/ul and Plt: 82267/ul. Bone marrow findings reflected >80% of prominent erythroid precursors with large irregular nuclei, dispersed chromatin, 1 to 3 elongated nucleoli, deeply basophilic cytoplasm, and an intense mitotic activity. Immunophenotypic features displayed erythroid clonality 90% (CD34, CD71, CD105, CD36, CD235) and myeloid clonality 1,4% (CD117, CD34). Conclusions. Among all AML cases, AEL prevalence percentage (14,1) is increased at high altitude (4000 m). Such increase may be due to the increase in HIF and erythropoietin at hypobaric hypoxia environment, so studying the mechanisms involved are of interest.