Human acute leukemia induced pluripotent stem cells: a unique model for investigating disease development and pathogenesis

Why Is Importance the Reprogramming and Remodeling In Malignant Hematopoietic Microenvironment and Its Hematopoietic Stem Cells Too

“…We know in MPN, pluripotent stem cell (PSC) can be involved, so induced pluripotent stem cell (iPSC) is a powerful tool for modeling key aspects of human disease. Indeed, iPSC from primary leukemic cells have been generated from chronic hematological malignancies like chronic myelocytic leukemia (CML), etc, but not reported for acute myeloid leukemia(AML) or acute lymphoblastic leukemia(ALL) to date, whereas iPSC has been generated from normal human myeloid, B and T cells too, and our data demonstrated that despite of multiple combinations of reprogramming factors could not be reprogrammed to pluripotency, but there are some challenges in reprogramming primary cancer cells, for example reprogramming process with human stromal cells to AML blasts may be possible [9][10][11][12][13][17][18][19][20].…”

“…Moreover, HSC of PV has an intrinsic defect which the stem cell defect alters a number of cellular functions and is not restricted to cytokine receptor signal transduction. On the other hand, some researchers observed a more complex remodeling of the clone in response to erythropoietin(EPO), actually the action of EPO on erythroid progenitors is known, but its direct action on hematopoietic stem and progenitor cells(HSPCs) is possible too [4,9,17], viz EPO does action on multi-potent progenitor (MPP) independent of the niche as well as modulates fate or varying in nature by remodeling at the clonal arrangement of MPP store (figure 2), which also could be one of the factors underlying the adverse side effects development during use of long term EPO in the therapy and high EPO levels with hematopoietic malignancy as well (9,17,(26)(27).…”

Generation of a Urine-Derived Ips Cell Line from a Patient with a Ventricular Septal Defect and Heart Failure and the Robust Differentiation of These Cells to Cardiomyocytes via Small Molecules

“…The method of disease modeling with patient-specific iPSCs can be applied to all types of chromosomal inherited diseases, from monogenetic to complex polygenetic disorders [25][26][27][28]. iPSCs hold great promise for disease modeling and regenerative therapies.…”

Genetics and epigenetics of leukemia and lymphoma: from knowledge to applications, meeting report of the Josep Carreras Leukaemia Research Institute

“…Taking a broad, multilayer omics approach, his findings have revealed the genetic and epigenetic evolution of a TCF3‐ 67 ZNF384/PTPN11‐ driven clone in twins with BCP‐ALL, which supports the hypothesis that a pre‐VDJ primitive fetal hematopoietic progenitor or stem cell is the COO of TCF3‐ZNF384 and PTPN11 mutations. Menéndez also drew attention to the great effort expended on mimicking this leukemia in vitro …”