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Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone
- Source :
- Leukemia. 30:776-781
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Interferon alpha (IFN-α) has been used for over 30 years to treat myeloproliferative neoplasms (MPNs). IFN-α was shown to induce clinical, hematological, molecular and histopathological responses in small clinical studies. Such combined efficacy has never been achieved with any other drug to date in such a significant proportion of patients. However, toxicity remains a limitation to its broader use despite the development of pegylated forms with better tolerance. Several on going phase 3 studies of peg- IFN-α versus hydroxyurea will help to define its exact place in MPN management. IFN-α efficacy is likely the consequence of a broad range of biological properties, including enhancement of immune response, direct effects on malignant cells and ability to cycle dormant malignant stem cells. However, comprehensive elucidation of its mechanism of action is still lacking. Sustained clinical, molecular and morphological responses after IFN-α discontinuation raised the hope that this drug could eradicate MPN. There is now consistent evidence showing that IFN-α is able to eliminate malignant clones harboring JAK2V617F or Calreticulin mutations. However, the molecular complexity of these diseases could hamper IFN-α efficacy, as the presence of additional non-driver mutations, like in the TET2 gene, could be associated with resistance to IFN-α. Therefore, combined therapy with another targeted agent could be required to eradicate MPN, and the best IFN-α companion for achieving this challenge remains to be determined.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Clone (cell biology)
Alpha interferon
Antiviral Agents
03 medical and health sciences
0302 clinical medicine
Myeloproliferative Disorders
Internal medicine
medicine
Humans
Hematology
biology
Interferon-alpha
medicine.disease
Lymphoma
Leukemia
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Immunology
biology.protein
Cancer research
Stem cell
Calreticulin
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....932b6e3c725a9494f5036a0d309aec3e