CoChat
Sign Up
Cited by 80

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells.

Schemionek, Mirle, Elling, Christian, Steidl, Ulrich, Bäumer, Nicole, Hamilton, Ashley, Spieker, Tilmann, Göthert, Joachim R., Stehling, Martin, Wagers, Amy, Huettner, Claudia S., Tenen, Daniel G., Tickenbrock, Lara, Berdel, Wolfgang E., Serve, Hubert, Holyoake, Tessa L., Müller-Tidow, Carsten, Koschmieder, Steffen·2010·Blood
DOI 10.1182/blood-2009-04-215376
Open this paper in CoChat — free account

Abstract

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. The phenotype 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2009-04-215376

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 6 references

Research works printed but not linked: 38

  1. Fialkow, 1977, Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage., Am J Med, 63, 125, 10.1016/0002-9343(77)90124-3 · DOI
  2. Takahashi, 1998, Lineage involvement of stem cells bearing the Philadelphia chromosome in chronic myeloid leukemia in the chronic phase as shown by a combination of fluorescence-activated cell sorting and fluorescence in situ hybridization., Blood, 92, 4758, 10.1182/blood.V92.12.4758 · DOI
  3. Daley, 1990, Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome., Science, 247, 824, 10.1126/science.2406902 · DOI · Paper page
  4. Heisterkamp, 1990, Acute leukaemia in bcr/abl transgenic mice., Nature, 344, 251, 10.1038/344251a0 · DOI
  5. Li, 1999, The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity., J Exp Med, 189, 1399, 10.1084/jem.189.9.1399 · DOI
  6. Koschmieder, 2005, Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis., Blood, 105, 324, 10.1182/blood-2003-12-4369 · DOI · Paper page
  7. Ren, 2005, Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia., Nat Rev Cancer, 5, 172, 10.1038/nrc1567 · DOI · Paper page
  8. Druker, 2006, Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia., N Engl J Med, 355, 2408, 10.1056/NEJMoa062867 · DOI
  9. Kantarjian, 2006, Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL., N Engl J Med, 354, 2542, 10.1056/NEJMoa055104 · DOI
  10. O'Hare, 2007, Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia., Blood, 110, 2242, 10.1182/blood-2007-03-066936 · DOI
  11. Copland, 2008, BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors., Blood, 111, 2843, 10.1182/blood-2007-09-112573 · DOI
  12. Bhatia, 2003, Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment., Blood, 101, 4701, 10.1182/blood-2002-09-2780 · DOI
  13. Huntly, 2004, MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors., Cancer Cell, 6, 587, 10.1016/j.ccr.2004.10.015 · DOI · Paper page
  14. Hu, 2006, Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice., Proc Natl Acad Sci U S A, 103, 16870, 10.1073/pnas.0606509103 · DOI
  15. Dazzi, 1998, The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: an in vivo model of chronic myelogenous leukemia biology., Blood, 92, 1390, 10.1182/blood.V92.4.1390 · DOI
  16. Dazzi, 2000, Normal and chronic phase CML hematopoietic cells repopulate NOD/SCID bone marrow with different kinetics and cell lineage representation., Hematol J, 1, 307, 10.1038/sj.thj.6200051 · DOI
  17. Eisterer, 2005, Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease., Leukemia, 19, 435, 10.1038/sj.leu.2403649 · DOI
  18. Petzer, 1997, Selective expansion of primitive normal hematopoietic cells in cytokine-supplemented cultures of purified cells from patients with chronic myeloid leukemia., Blood, 90, 64, 10.1182/blood.V90.1.64 · DOI
  19. Gishizky, 1993, Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice., Proc Natl Acad Sci U S A, 90, 3755, 10.1073/pnas.90.8.3755 · DOI
  20. Ivanova, 2002, A stem cell molecular signature., Science, 298, 601, 10.1126/science.1073823 · DOI
  21. Jiang, 2007, Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies., Leukemia, 21, 926, 10.1038/sj.leu.2404609 · DOI
  22. Neering, 2007, Leukemia stem cells in a genetically defined murine model of blast-crisis CML., Blood, 110, 2578, 10.1182/blood-2007-02-073031 · DOI · Paper page
  23. Kelly, 2007, Tumor growth need not be driven by rare cancer stem cells., Science, 317, 337, 10.1126/science.1142596 · DOI
  24. Somervaille, 2006, Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia., Cancer Cell, 10, 257, 10.1016/j.ccr.2006.08.020 · DOI · Paper page
  25. Ishii, 2005, In vivo characterization of bone marrow-derived fibroblasts recruited into fibrotic lesions., Stem Cells, 23, 699, 10.1634/stemcells.2004-0183 · DOI
  26. Skorski, 2008, BCR/ABL, DNA damage and DNA repair: implications for new treatment concepts., Leuk Lymphoma, 49, 610, 10.1080/03093640701859089 · DOI
  27. Eaves, 1993, Culture purging in leukemia: past, present, and future., Leuk Lymphoma, 11, 259, 10.3109/10428199309047896 · DOI
  28. Wu, 2007, Imaging hematopoietic precursor division in real time., Cell Stem Cell, 1, 541, 10.1016/j.stem.2007.08.009 · DOI
  29. Punzel, 2003, The symmetry of initial divisions of human hematopoietic progenitors is altered only by the cellular microenvironment., Exp Hematol, 31, 339, 10.1016/S0301-472X(03)00024-9 · DOI
  30. Neviani, 2005, The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein., Cancer Cell, 8, 355, 10.1016/j.ccr.2005.10.015 · DOI
  31. Jorgensen, 2007, Characterization of cancer stem cells in chronic myeloid leukaemia., Biochem Soc Trans, 35, 1347, 10.1042/BST0351347 · DOI
  32. Colijn, 2005, A mathematical model of hematopoiesis: I. Periodic chronic myelogenous leukemia., J Theor Biol, 237, 117, 10.1016/j.jtbi.2005.03.033 · DOI
  33. Nowicki, 2004, BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks., Blood, 104, 3746, 10.1182/blood-2004-05-1941 · DOI
  34. Slupianek, 2006, BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells., DNA Repair (Amst), 5, 243, 10.1016/j.dnarep.2005.10.005 · DOI
  35. Koptyra, 2008, BCR/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress., Leukemia, 22, 1969, 10.1038/leu.2008.78 · DOI
  36. Merante, 2005, Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation., Haematologica, 90, 979
  37. Ali, 2005, Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML): outcome of discontinuation of imatinib therapy after achieving a molecular remission., Leuk Res, 29, 971, 10.1016/j.leukres.2005.01.009 · DOI
  38. Breccia, 2006, Discontinuation of imatinib therapy after achievement of complete molecular response in a Ph(+) CML patient treated while in long lasting complete cytogenetic remission (CCR) induced by interferon., Leuk Res, 30, 1577, 10.1016/j.leukres.2006.03.011 · DOI

Cited by

See all 80

Metadata

Authors
Schemionek, M., Elling, C., Steidl, U., Bäumer, N., Hamilton, A., Spieker, T., Göthert, J. R., Stehling, M., Wagers, A., Huettner, C. S., Tenen, D. G., Tickenbrock, L., Berdel, W. E., Serve, H., Holyoake, T. L., Müller-Tidow, C., & Koschmieder, S.
Affiliations
  • Department of Medicine, Hematology and Oncology, University of Münster, Münster, Germany;
  • Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY;
  • Section of Experimental Haematology, University of Glasgow, Glasgow, United Kingdom;
  • Department of Pathology, University of Münster, Münster, Germany;
  • Department of Hematology, University of Duisburg-Essen, Essen, Germany;
  • Max-Planck-Institute of Molecular Biomedicine, Münster, Germany;
  • Joslin Diabetes Center, Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Boston, MA;
  • Department of Molecular Oncology, Dana-Farber Cancer Institute, Boston, MA;
  • Harvard Stem Cell Institute, Harvard Medical School, Boston, MA and Cancer Science Institute, National University of Singapore, Singapore;
  • University of Applied Science, Hochschule Hamm-Lippstadt, Hamm, Germany; and
  • Department of Medicine, Hematology and Oncology, University of Frankfurt, Frankfurt, Germany
Venue
Blood
Publisher
American Society of Hematology
Published
2010-04-22
Volume
115
Issue
16
Pages
3185-3195
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2009-04-215376
Cited by
80
References
6
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. https://app.cochat.ai/papers/10.1182/blood-2009-04-215376
The paper
Schemionek, M., Elling, C., Steidl, U., Bäumer, N., Hamilton, A., Spieker, T., Göthert, J. R., Stehling, M., Wagers, A., Huettner, C. S., Tenen, D. G., Tickenbrock, L., Berdel, W. E., Serve, H., Holyoake, T. L., Müller-Tidow, C., & Koschmieder, S. (2010). BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood. https://doi.org/10.1182/blood-2009-04-215376