Aggressive myeloid leukemia formation is directed by the Musashi 2/Numb pathway

@article{Griner2010AggressiveML,
  title={Aggressive myeloid leukemia formation is directed by the Musashi 2/Numb pathway},
  author={L. Griner and G. Reuther},
  journal={Cancer Biology \& Therapy},
  year={2010},
  volume={10},
  pages={979 - 982}
}
Chronic myeloid leukemia (CML) progresses from a chronic phase to a deadly blast crisis phase. While it is known that BCR-ABL initiates the disease and that secondary molecular and genetic abnormalities likely contribute to progression of the disease to blast crisis, details regarding the mechanism(s) of blast phase progression are lacking. Two recent reports identify Musashi 2 (Msi2) as a key regulator in the progression of CML from the chronic phase to blast crisis. These reports demonstrated… Expand
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References

SHOWING 1-10 OF 30 REFERENCES
Regulation of myeloid leukemia by the cell fate determinant Musashi
TLDR
The data show that the Musashi–Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias. Expand
The biology of CML blast crisis.
TLDR
Validation of the critical role of certain secondary changes (ie, loss of p53 or C/EBPalpha function) in murine models of CML blast crisis and in in vitro assays of BCR/ABL transformation of human hematopoietic progenitors might lead to the development of novel therapies based on targeting BCR /ABL and inhibiting or restoring the gene activity gained or lost during disease progression. Expand
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
TLDR
It is demonstrated that Msi2 is the predominant form expressed in hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo and Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease. Expand
Oncogenic interaction between BCR-ABL and NUP98-HOXA9 demonstrated by the use of an in vitro purging culture system.
TLDR
Evidence is provided of high levels of HOXA9 expressed in leukemic blasts from acute-phase CML patients and that it interacts significantly on a genetic level with BCR-ABL in the authors' in vivo CML model, which supports a causative, as opposed to a consequential, role for NUP98-HOXA 9 (and possibly HOX a9) in CML disease progression. Expand
A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9
Constitutive activation of tyrosine kinases, such as the BCR/ABL fusion associated with t(9;22)(q34;q22), is a hallmark of chronic myeloid leukemia (CML) syndromes in humans. Expression of BCR/ABL isExpand
Leukemia stem cells in a genetically defined murine model of blast-crisis CML.
TLDR
A mouse model provides a powerful means by which the in vivo behavior of LSCs versus HSCs can be characterized and candidate treatment regimens can be optimized for maximal specificity toward primitive leukemia cells. Expand
NUP98 Dysregulation in Myeloid Leukemogenesis
  • M. A. S. MOORE, K. Y. CHUNG, +4 authors G. Morrone
  • Biology, Medicine
  • Annals of the New York Academy of Sciences
  • 2007
TLDR
Transduction of NUP98 fusion genes into human CD34+ cells confers a proliferative advantage in long‐term cytokine‐stimulated and stromal cocultures and in NOD‐SCID engrafted mice, associated with a five‐ to eight‐fold increase in hematopoietic stem cells. Expand
NUP98–HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice
TLDR
Hemopoietic chimeras serving as a mouse model for NUP98–HOXA9‐induced leukemia reproduced several of the phenotypes observed in human disease, illustrating the complexity of leukemic transformation. Expand
Expression of the NUP98/HOXA9 fusion transcript in the blast crisis of Philadelphia chromosome‐positive chronic myelogenous leukaemia with t(7;11)(p15;p15)
TLDR
Reverse transcriptase polymerase chain reaction identified the NUP98/HOXA9 transcript, suggesting that the Nup98/ HOXA 9 fusion protein could play a critical role in the progression to blast crisis. Expand
Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia.
TLDR
Results using BCR-ABL mutants which specifically uncouple connections to known signal transduction pathways show that STAT5 activation is kinase dependent and correlates directly with ability to confer cytokine independent growth in hematopoietic cells. Expand
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