Featured
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Article |
Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms
Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.
- Ashok Kumar Jayavelu
- , Tina M. Schnöder
- & Florian H. Heidel
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Article |
Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.
- Erik L. Bao
- , Satish K. Nandakumar
- & Vijay G. Sankaran
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Article |
Somatic mutations and cell identity linked by Genotyping of Transcriptomes
Profiling of over 38,000 CD34+ cells from patients with CALR-mutated myeloproliferative neoplasms, using the ‘Genotyping of Transcriptomes’ procedure, reveals that the transcriptional output of these mutations depends upon native cell identity.
- Anna S. Nam
- , Kyu-Tae Kim
- & Dan A. Landau
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Letter |
Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy
Chronic exposure to JAK2 inhibitors leads to reactivation of downstream signalling through the formation of heterodimers between JAK2 and other JAK kinases in myeloproliferative neoplasms, which can be overcome with Hsp90 inhibitors.
- Priya Koppikar
- , Neha Bhagwat
- & Ross L. Levine
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Letter |
Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2
The TET family of enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Mutations in the gene encoding TET2 are frequently observed in myeloid malignancies. Here it is shown that these disease-associated mutations compromise TET2 catalytic activity; bone marrow samples from patients with TET2 mutations have low levels of 5hmC in genomic DNA, and TET2 is required for normal haematopoietic differentiation. Measurement of genomic 5hmC levels may prove valuable as a diagnostic tool in myeloid cancers.
- Myunggon Ko
- , Yun Huang
- & Anjana Rao