Impact of interferon on a triple positive polycythemia vera

Campario, Hugo; Mosca, Matthieu; Aral, Bernard; Bourgeois, Valentin; Martin, Pauline; Brustel, Antoine; Filser, Mathilde; Marzac, Christophe; Plo, Isabelle; Girodon, François

doi:10.1038/s41375-019-0636-0

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…We detected 32 MPN patients with JAK2 V617F , 12 with CALR m (7 type 1 and 5 type 2), 2 with MPL W515K/R , one having both JAK2 V617F and CALR del46 and one having JAK2 V617F , CALR del52 and MPL S505N (Figure 2A and B). We classified the last two cases as CALR m MPN because the CALR m VAF > 0.4 were clearly dominant 21 and because the JAK2 V617F and CALR m were mutually exclusive in progenitors (Figure S1). Next generation sequencing of a myeloid-focused panel of 77 genes using genomic DNA isolated from granulocytes identified additional mutations in 31% of these cases (Figure 2C).…”

Section: Study Of Mpn Prospective Cohort Treated With Ifnαmentioning

confidence: 99%

Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms

Mosca

Hermange

Tisserand

et al. 2021

Blood

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Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells (HSC) caused mainly by recurrent mutations in genes encoding JAK2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL). Interferon alpha (IFNα) has demonstrated some efficacy in inducing molecular remission in MPN. In order to determine factors that influence molecular response rate, we evaluated the long-term molecular efficacy of IFNα in MPN patients by monitoring the fate of cells carrying driver mutations in a prospective observational and longitudinal study of 48 patients over more than 5 years. We measured several times per year the clonal architecture of early and late hematopoietic progenitors (84,845 measurements) and the global variant allele frequency in mature cells (409 measurements). Using mathematical modeling and hierarchical Bayesian inference, we further inferred the dynamics of IFNα-targeted mutated HSC. Our data support the hypothesis that IFNα targets JAK2V617F HSC by inducing their exit from quiescence and differentiation into progenitors. Our observations indicate that treatment efficacy is higher in homozygous than heterozygous JAK2V617F HSC and increases with high IFNα dosage in heterozygous JAK2V617F HSC. Besides, we found that the molecular responses of CALRm HSC to IFNα were heterogeneous, varying between type 1 and type 2 CALRm, and high dosage of IFNα correlates with worse outcomes. Together, our work indicates that the long-term molecular efficacy of IFNα implies an HSC exhaustion mechanism and depends on both the driver mutation type and IFNα dosage.

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Section: Study Of Mpn Prospective Cohort Treated With Ifnαmentioning

confidence: 99%

Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms

Mosca

Hermange

Tisserand

et al. 2021

Blood

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“…Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs) share three common driver mutations in the Janus kinase 2 ( JAK2 ), calreticulin ( CALR ) and myeloproliferative leukaemia oncogene ( MPL ) genes 1 . Although these driver mutations are thought to be mutually exclusive, rare cases of MPN with two or more co‐existing driver mutations have been reported: JAK2 V617F/ JAK2 exon 12, 2 JAK2 V617F/ CALR , 2–8 JAK2 V617F/ MPL , 2,4,7,9–11 CALR / MPL 2,12,13 and JAK2 V617F/ CALR / MPL 14 . Clonogenic evaluation studies indicated these mutations mostly co‐existed in separate clones.…”

Section: Mutation Calr+ Jak2 Wt Calr+ Jak2 V617f+mentioning

confidence: 99%

Acquisition of JAK2 V617F to CALR‐mutated clones accelerates disease progression and might enhance growth capacity

Nishimura¹,

Nagaharu

Itō

et al. 2021

Br J Haematol

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In summary, we report the largest case series of daratumumab for the treatment of refractory autoimmune cytopenias. Our data demonstrate acceptable response rates (66%) with durable responses in most responders. Our report has several limitations including its retrospective nature and variable dosing schedules. Larger prospective studies are needed to study daratumumab for refractory autoimmune cytopenias.

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2020

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Impact of interferon on a triple positive polycythemia vera

Cited by 4 publications

References 10 publications

Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms

Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms

Acquisition of JAK2 V617F to CALR‐mutated clones accelerates disease progression and might enhance growth capacity

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