Current pre-clinical and clinical advances in the BCR-ABL1-positive and -negative chronic myeloproliferative neoplasms

Mughal, Tariq I.; Vannucchi, Alessandro M.; Soverini, Simona; Bazeos, Alexandra; Tibes, Raoul; Saglio, Giuseppe; Abdel-Wahab, Omar; Pardanani, Animesh; Hehlmann, Rüdiger; Barbui, Tiziano; Etten, Richard Van; Tefferi, Ayalew; Goldman, John M.

doi:10.3324/haematol.2013.097832

Cited by 5 publications

(4 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A minority of patients achieve a deeper molecular response with more than 4-log or 4.5-log reduction in BCR-ABL1 transcripts [referred to as MR 4.0 and MR, 4.5 respectively; MR 4.5 was previously referred to as a complete molecular response (CMR)] (Table 1). 73,74 These results were confirmed by independent single centers as well as company-led registration studies. 75 It should also be said that the success of these and other CML treatment studies epitomize the critical importance of an optimal molecular monitoring methodology (see below).…”

supporting

confidence: 70%

Chronic myeloid leukemia: reminiscences and dreams

et al. 2016

Self Cite

View full text Add to dashboard Cite

supporting

confidence: 70%

Chronic myeloid leukemia: reminiscences and dreams

et al. 2016

Self Cite

View full text Add to dashboard Cite

“…53 Aberrations in ASXL1, EZH2, SRSF2 and IDH1/2 appear to have a predictive impact on the overall and leukemia-free survival, suggesting that the MPN epigenome is clinically relevant; the greatest impact appears to be with the ASXL1 mutation. 13,53 In addition, promoter-specific hypermethylation of candidate genes such as the chemokine receptor CXCR4 has been linked to the constitutive migration of CD34 + cells in PMF. 54 Global methylation profiling in MF revealed a distinct methylation signature, and in patients who transform to AML, it has been noted that the number of differentially methylated regions increase significantly and the aberrant genes are involved in the 'IFN pathway'.…”

Section: Impact Of Targeting the Jak/signal Transducers And Activatormentioning

confidence: 99%

“…10 Current clinical experience, however, has not yielded as impressive results with JAK2 inhibitors, but rather a qualified progress leading to the licensing of ruxolitinib, a selective JAK1 and JAK2 inhibitor, for patients with advanced MF. [11][12][13] The drug affords substantial symptomatic benefits, reduction in splenomegaly and improved survival, but has no significant impact on the malignant clone. Furthermore, 50% of patients discontinue ruxolitinib therapy at 3 years due to loss of clinical benefit or adverse side effects.…”

Section: Introductionmentioning

confidence: 99%

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Tamari

Mughal

Rondelli

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

At present, allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment for patients with myelofibrosis (MF). Unfortunately a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at time of diagnosis. The approval of the first JAK inhibitor, Ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support to assess the drug’s candidacy in the peri-transplant period. The drug’s precise impact on clinical outcome following allo-SCT is currently not known; nor is the drug’s long term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who are undergoing allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology’s meeting in New Orleans, USA, on 6th December 2013 and the European Hematology Association meeting in Milan, Italy on 13th June 2014. This document summarizes the results of these efforts.

show abstract

“…As knowledge on these disorders continues to evolve, new preclinical and clinical challenges have been identified [1]. Following the unraveling of the molecular pathogenesis of CML in the 1980s, tyrosine kinase inhibitors (TKIs) entered the clinic for patients with chronic myeloid leukemia (CML) [2–4].…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the biology and treatment of chronic myeloproliferative neoplasms

Mughal¹,

Barbui²,

Abdel‐Wahab³

et al. 2014

Leukemia & Lymphoma

View full text Add to dashboard Cite

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoiesis characterized by a high frequency of genetic alterations and include chronic myeloid leukemia (CML) and the BCR-ABL1-negative MPNs. Herein we summarize recent advances and controversies in our understanding of the biology and therapy of these disorders, as discussed at the 8th post-American Society of Hematology CML-MPN workshop. The principal areas addressed include the breakthrough discovery of CALR mutations in patients with JAK2/MPL wild type MPN, candidate therapies based on novel genetic findings in leukemic transformation and new therapeutic targets in MPNs, and an appraisal of bone marrow histopathology in MPNs with a focus on the potential new clinical entity of “ masked ” polycythemia vera. An update on clinical trials of Janus kinase (JAK) inhibitors is presented as well as current understanding regarding the definitions and mechanisms of resistance to JAK inhibitors, and updated information on the safety and efficacy of discontinuation of tyrosine kinase inhibitors in patients with CML.

show abstract

Current pre-clinical and clinical advances in the BCR-ABL1-positive and -negative chronic myeloproliferative neoplasms

Cited by 5 publications

References 39 publications

Chronic myeloid leukemia: reminiscences and dreams

Chronic myeloid leukemia: reminiscences and dreams

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Novel insights into the biology and treatment of chronic myeloproliferative neoplasms

Contact Info

Product

Resources

About