Prognostic effect of calreticulin mutations in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

Panagiota, Victoria; Thol, Felicitas; Markus, Birgit; Fehse, Boris; Alchalby, Haefaa; Badbaran, Anita; Lehmann, Ulrich; Koenecke, Christian; Shahswar, Rabia; Chaturvedi, Anuhar; Stadler, Michael; Eder, Matthias; Göhring, Gudrun; Koenigsmann, Michael; Kloos, Arnold; Trummer, Arne; Schroeder, Thomas; Kobbe, Guido; Thiede, Christian; Platzbecker, Uwe; Schlegelberger, Brigitte; Hh, Kreipe; Ganser, Arnold; Kröger, Nicolaus; Heuser, Michael

doi:10.1038/leu.2014.66

Cited by 57 publications

(51 citation statements)

References 15 publications

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“…There is one preliminary report suggestive of best outcomes in CALR positive and worst outcomes in JAK2/MPL/CALR-negative ('triple-negative') patients following allo-SCT. 97 In this effort comprising of 119 patients with MF, a multivariable analysis revealed shorter survival and higher NRM for the 'triple-negative' cohort compared to patients with any mutations. These observations have now been validated by several recent efforts confirming the notion of patients with JAK2 wild type (WT), MPL WT and CALR WT, to have poor outcomes.…”

Section: Variablementioning

confidence: 87%

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

Tamari

Mughal

Rondelli

et al. 2015

Bone Marrow Transplant

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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.

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Section: Variablementioning

confidence: 87%

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

Tamari

Mughal

Rondelli

et al. 2015

Bone Marrow Transplant

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“…Эта мутация имеется более чем у 95 % больных истинной полицитемией, но только не более чем у 50 % пациентов с ПМФ. Контролируемое JAK2 V617F семейство белков STAT активно фосфорили-руется [3][4][5][6]. При другой (точечной) мутации, которая встречается у больных ПМФ и эссенциальной тромбо-цитемией, происходит замена аминокислоты в позиции 515 молекулы рецептора тромбопоэтина c-MPL (W515L, W515K), что также приводит к активации сигнального пути JAK2-STAT [4].…”

Section: V617funclassified

“…Позже было показано, что у больных ПМФ наблюдается гиперэкспрессия локализованного на хромосоме 19 гена PVR-1 или NB1, которые, в свою очередь, ответственны за экспрессию антигена CD177 [7]. Наконец, недавно установлено, что 1 / 3 больных ПМФ свойственны диагностически и патогенетически значимые точечные мутации гена кальретикулина (CALR) [3][4][5][6].…”

Section: V617funclassified

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New Сytogenetic Approaches in Patients with Primary Myelofibrosis

Tl¹,

Мамаев²,

Байков³

et al. 2016

Clin oncohematol

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“…17 In general, triple-negative patients (JAK2V617F, CALR, MPL) demonstrate inferior survival compared with those carrying the mutations. 18 Despite our advances, the true role of molecular status in choice of MPN therapy is evolving and requires further validation before routine application.…”

Section: When To Treat? New Mpn Molecular Insightsmentioning

confidence: 99%

Therapy for myeloproliferative neoplasms: when, which agent, and how?

Geyer¹,

Mesa

2014

Hematology

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Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs. Learning Objectives• To recognize the symptomatic burden present in lower-risk MPN populations and the role that targeted treatments may play in addressing this • To review the spectrum of available MPN-targeted treatments and the data involving their synergistic use with conventional treatments

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Prognostic effect of calreticulin mutations in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

Cited by 57 publications

References 15 publications

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

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

New Сytogenetic Approaches in Patients with Primary Myelofibrosis

Therapy for myeloproliferative neoplasms: when, which agent, and how?

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