Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

TSPO2 translocates 5‐aminolevulinic acid into human erythroleukemia cells

“…Exogenous ALA bypasses the rate limiting enzyme ALA synthase and accelerates heme synthesis. ALA induced erythroid differentiation of human myelogenous leukaemia K562 [Fujiwara et al, 2014] and murine erythroleukemia MEL cells, leading to cell hemoglobinisation [Malik et al, 1988].…”

“…Different cell models are available to study ALA-induced erythroid differentiation. (i) K562 presents characteristics of early erythroid differentiation states [Fujiwara et al, 2014]. (ii) Erythropoietin (EPO)-dependent UT-7 cells display erythroid properties characteristic of more advanced erythroid differentiation states [Komatsu et al, 1993].…”

Five‐aminolevulinic acid: New approach for congenital sideroblastic anemia

“…With the exception of pyridoxine‐responsive patients, therapy for CSA has been mainly supportive. Given that ALA supplementation, theoretically, could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects, we investigated the safety and efficacy of ALA treatment. This study was approved by the Institutional Review Board of Matsushita Memorial Hospital.…”

“…The measurements were done after the first dose of the day. ALA blood concentration reached an effective level (>10 μmol/L; defined in in vitro experiments using K562, an erythroid leukemia cell line), for approximately 2 h per day. The calculated area under the ALA and the PPIX curves through 0–24 h was 39.4 and 0.39 μmol‐h/L in the present case, respectively.…”

“…The patient was given a dose equal to approximately half the amount of endogenous synthesis (approx. 700 mg) in a healthy adult by ubiquitously expressed ALAS1 and erythroid‐specific ALAS2 daily, resulting in an ALA blood concentration at the effective level (>10 μmol/L; defined according to in vitro experiments). The increased levels of not only ALA but also PPIX accruing from exogenous ALA‐phosphate suggested that a certain level of heme was synthesized in the patient.…”