Blood, 22 April 2010, vol.115, no.16, pp.3185-3195
BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells
First author和corresponding author是University of Münster, Germany的研究者~不過作者群有很多其它研究機構的，包括Albert Einstein college of medicine、University of Glasgow, Max-Plank-institute of molecular biomedicine, Harvard等。
In a previously developed inducible transgenic mouse model of chronic myeloid leukemia, we now demonstrate that the disease is transplantable using BCR-ABL+ Lin–Sca-1+c-kit+ (LSK) cells. Interestingly, the phenotype is more severe when unfractionated bone marrow cells are transplanted, yet neither progenitor cells (Lin–Sca-1–c-kit+), nor mature granulocytes (CD11b+Gr-1+), nor potential stem cell niche cells (CD45–Ter119–) are able to transmit the disease or alter the phenotype. Thephenotype is largely independent of BCR-ABL priming before transplantation. However, prolonged BCR-ABL expression abrogates the potential of LSK cells to induce full-blown disease in secondary recipients and increases the fraction of multipotent progenitor cells at the expense of long-term hematopoietic stem cells (LT-HSCs) in the bone marrow. BCR-ABL alters the expression of genes involved in proliferation, survival, and hematopoietic development, probably contributing to the reduced LT-HSC frequency within BCR-ABL+ LSK cells. Reversion of BCR-ABL, or treatment with imatinib, eradicates mature cells, whereas leukemic stem cells persist, giving rise to relapsed chronic myeloid leukemia on reinduction of BCR-ABL, or imatinib withdrawal. Our results suggest that BCR-ABL induces differentiation of LT-HSCs and decreases their self-renewal capacity.
因為我的英文不好啦..
最後就是說BCR-ABL這個fusion gene，aka philadelphia chromosome, 是Chronic myelogenous leukemia(CML)中最常見的染色體異常，主因為t(9;22)轉位，造成的BCR-ABL fusion.
這篇主要是 在講BCR-ABL可以造成long term hematopoietic stem cell的分化，並降低該血液幹細胞的自我更新能力。
