Morgana acts as an oncosuppressor in chronic myeloid leukemia.

@article{DiSavino2015MorganaAA,
  title={Morgana acts as an oncosuppressor in chronic myeloid leukemia.},
  author={Augusta Di Savino and Cristina Panuzzo and Stefania La Rocca and Ubaldo Familiari and Rocco Piazza and Sabrina Crivellaro and Giovanna Carr{\`a} and Roberta Ferretti and Federica Fusella and Emilia Giugliano and Annalisa Camporeale and Irene Franco and Barbara Miniscalco and Juan Carlos Cutrin and E. Guimar{\~a}es Do Turco and Lorenzo Silengo and Emilio Hirsch and Giovanna Rege-Cambrin and Carlo B Gambacorti-Passerini and P. P. Pandolfi and Mauro Giulio Papotti and Giuseppe Saglio and Guido Tarone and Alessandro Morotti and Mara Brancaccio},
  journal={Blood},
  year={2015},
  volume={125 14},
  pages={
          2245-53
        }
}
We recently described morgana as an essential protein able to regulate centrosome duplication and genomic stability, by inhibiting ROCK. Here we show that morgana (+/-) mice spontaneously develop a lethal myeloproliferative disease resembling human atypical chronic myeloid leukemia (aCML), preceded by ROCK hyperactivation, centrosome amplification, and cytogenetic abnormalities in the bone marrow (BM). Moreover, we found that morgana is underexpressed in the BM of patients affected by atypical… 

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References

SHOWING 1-10 OF 62 REFERENCES
Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML.
BACKGROUND The molecular causes of many hematologic cancers remain unclear. Among these cancers are chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL1-negative) chronic myeloid leukemia
Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions.
TLDR
Various combinations of mutations suggest a multistep pathogenesis and may account for clinical heterogeneity, and the prognostic and diagnostic significance of these molecular lesions, in particular their value as biomarkers of response or resistance to specific therapies, while uncertain now is likely to be clarified as large systematic studies come to completion.
Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis.
Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability
TLDR
The results indicate that centrosome defects are a common and early detectable feature in CML that may contribute to acquisition of chromosomal aberrations and aneuploidy.
Recurrent SETBP1 mutations in atypical chronic myeloid leukemia
Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic
Morgana acts as a proto‐oncogene through inhibition of a ROCK–PTEN pathway
TLDR
It is demonstrated that high morgana expression in different breast cancer subtypes correlates with high tumour grade, mitosis number, and lymph node positivity and, from a mechanistic point of view, causes PTEN destabilization, by inhibiting ROCK activity, hence triggering the PI3K/AKT survival pathway.
Atypical chronic myeloid leukaemia with trisomy 13: a case report.
Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.
TLDR
This study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders.
Rho-signaling pathways in chronic myelogenous leukemia.
TLDR
This review deals in detail with the known points of interference between Bcr-Abl and Rho kinase pathways and with the effects of Imatinib mesylate on Rho signaling and cell adhesion to the extracellular matrix (ECM) components.
...
1
2
3
4
5
...