Fetal origins of hematopoietic failure in a murine model of Fanconi anemia

Abstract

Key PointsFancc −/− mice experience previously unrecognized late gestational lethality. Fancc −/− fetal mouse hematopoiesis is quantitatively and qualitatively deficient.

Pluripotent Cell Models of Fanconi Anemia Identify the Early Pathological Defect in Human Hemoangiogenic Progenitors

“…Although accelerated apoptosis and cell cycle arrest in hematopoietic stem/ progenitor cells have been associated with BMF in patients with FA [5], precisely how and when the initial event that causes this consequence occurs have been unclear. Recent reports have indicated that the fate of hematopoietic progenitors has already been determined during fetal liver hematopoiesis both in humans and in mouse models of FA [5,6]. However, tracing the earlier developmental events to capture the initial event is both technically and ethically impossible at present in humans.…”

Altered Calcium and Red-ox homeostasis underline defective haematopoiesis in Fanconi Anemia

“…Significant depletion of the CD34+ fraction was observed in very young FA patients, well before the onset of pancytopenia suggesting the developmental origin of the FA stem cell defect [9] . Animal model experiments do support this concept [10,11,12,13] . Thus FA phenotype impacts HSC pool expansion and seeding of the fetal BM niche during development.…”

Genetic diagnosis of Fanconi anemia. Literature review

“…Накопление дефектов ДНК после рождения в результате различных физико-химических воздействий усугубляет нарушение гемо-поэза. Кроме выраженного апоптоза ранних гемато-логических предшественников происходит нарушение базовых свойств стволовых кроветворных клеток -способности к самоподдержанию, пролиферации и диф-ференцировке в различные линии гемопоэза [50][51][52]. Генетическая нестабильность при АФ реализуется в повышенной частоте развития ряда опухолей, на-иболее частые -ОМЛ/миелодис плазия и плоскокле-точный рак головы и шеи, слизистых оболочек рта и мочеполового тракта -тканей, характеризующихся высокой пролиферативной активностью.…”