Normal vs. Malignant hematopoiesis: the complexity of acute leukemia through systems biology

摘要: Development of normal hematopoietic cells is an ordered multi-step process, tightly regulated by a complex network intrinsic factors and microenvironmental cues that control cell fate decisions within the bone marrow (BM) (Pelayo et al., 2012; Purizaca Boulais Frenette, 2015). During malignant hematological disorders, including acute leukemias (AL), uncontrolled differentiation precursors lymphoid or myeloid series sustains tumor growth at expense blood production. Moreover, selection dominance among leukemic clones occur while competing for niche resources creating abnormal BM microenvironments co-participate in pathobiology disease (Colmone 2008; Ayala 2009; Kim 2015; Vilchis-Ordonez Thus, due to complexity health impact AL (Gupta 2014), new strategies better predict population dynamics according genetics, clinical heterogeneous contexts may contribute understand its guide decreasing overall mortality. Mathematical modeling has emerged as powerful tool biomedical research because it enables simulation biological systems efficient generation testable hypotheses. In recent years, been addressed from novel view biology, resulting helpful stochastic deterministic models providing clearer understanding simplification ofmalignant clonal evolution processes (Vesely 2011; Amir 2013; Paguirigan However, fitted experimental data must strike balance between simplicity reality, so they can bring insights into scenarios. Here we discuss importance challenges incorporating microenvironment modeling, key element will interplay populations selective pressure leading hematopoiesis progression. By developing integrative tools mimic behavior polyclonal context marrow, learn about crucial mechanisms co-participating etiology progression disease.