BCR-ABL enhances differentiation of long-term HSCs

http://dx.doi.org/10.1182/blood-2009-04-215376

Blood, 22 April 2010, vol.115, no.16, pp.3185-3195

BCR-ABL Enhances Differentiation of Long-Term Hematopoietic Stem Cells
Mirle Schemionek1, Christian Elling1, Ulrich Steidl2,Nicole Bäumer1, Ashley Hamilton3, Tilmann Spieker4,Joachim R. Göthert5, Martin Stehling6, Amy Wagers7,Claudia S. Huettner8, Daniel G. Tenen9,Lara Tickenbrock10, Wolfgang E. Berdel1,Hubert Serve11, Tessa L. Holyoake3,Carsten Müller-Tidow1, and Steffen Koschmieder1

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。