Future therapies for the myeloproliferative neoplasms

Robyn Scherber, Ruben Mesa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ever since their description as "myeloproliferative syndromes" by William Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by the selective use of rather mundane, nonspecific therapies that rely on either antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of drug development and discovery for the MPNs after the description of the JAK2 V617F mutation and the role this constitutively active tyrosine kinase has in MPN pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are about to begin) testing for the inhibition of JAK2 in an attempt to improve the treatment of MPNs. Both primary myelofibrosis and myelofibrosis following essential thrombocythemia or polycythemia vera have been the targets of the most extensive testing of these agents to date. Responses to these oral JAK2 inhibitors have been primarily intended to reduce splenomegaly and meaningfully improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are limited. Toxicities have ranged from myelosuppression to significant diarrhea. Additional agents with other mechanisms of action are also targeting JAK2, including histone deacetylase inhibitors and mTOR inhibitors. The results of preliminary trials of JAK2 inhibitors in polycythemia vera and essential thrombocythemia have been mixed but are premature. Many questions remain as to the optimal JAK2 inhibitory strategy and the full extent of the benefit of single-agent JAK2 inhibition.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalCurrent Hematologic Malignancy Reports
Volume6
Issue number1
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Essential Thrombocythemia
Polycythemia Vera
Primary Myelofibrosis
Neoplasms
Williams Syndrome
Histone Deacetylase Inhibitors
Splenomegaly
Drug Discovery
Therapeutics
Protein-Tyrosine Kinases
Diarrhea
Histology
Bone Marrow
Alleles
Mutation

Keywords

  • Essential thrombocythemia
  • Jak2 inhibitors
  • Myelofibrosis
  • Myeloproliferative neoplasm
  • Polycythemia vera
  • Treatment

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Future therapies for the myeloproliferative neoplasms. / Scherber, Robyn; Mesa, Ruben.

In: Current Hematologic Malignancy Reports, Vol. 6, No. 1, 01.03.2011, p. 22-27.

Research output: Contribution to journalArticle

@article{46ce7fc4cb5949df86b3a1b5707a43b7,
title = "Future therapies for the myeloproliferative neoplasms",
abstract = "Ever since their description as {"}myeloproliferative syndromes{"} by William Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by the selective use of rather mundane, nonspecific therapies that rely on either antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of drug development and discovery for the MPNs after the description of the JAK2 V617F mutation and the role this constitutively active tyrosine kinase has in MPN pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are about to begin) testing for the inhibition of JAK2 in an attempt to improve the treatment of MPNs. Both primary myelofibrosis and myelofibrosis following essential thrombocythemia or polycythemia vera have been the targets of the most extensive testing of these agents to date. Responses to these oral JAK2 inhibitors have been primarily intended to reduce splenomegaly and meaningfully improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are limited. Toxicities have ranged from myelosuppression to significant diarrhea. Additional agents with other mechanisms of action are also targeting JAK2, including histone deacetylase inhibitors and mTOR inhibitors. The results of preliminary trials of JAK2 inhibitors in polycythemia vera and essential thrombocythemia have been mixed but are premature. Many questions remain as to the optimal JAK2 inhibitory strategy and the full extent of the benefit of single-agent JAK2 inhibition.",
keywords = "Essential thrombocythemia, Jak2 inhibitors, Myelofibrosis, Myeloproliferative neoplasm, Polycythemia vera, Treatment",
author = "Robyn Scherber and Ruben Mesa",
year = "2011",
month = "3",
day = "1",
doi = "10.1007/s11899-010-0068-4",
language = "English (US)",
volume = "6",
pages = "22--27",
journal = "Current Hematologic Malignancy Reports",
issn = "1558-8211",
publisher = "Springer Science + Business Media",
number = "1",

}

TY - JOUR

T1 - Future therapies for the myeloproliferative neoplasms

AU - Scherber, Robyn

AU - Mesa, Ruben

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Ever since their description as "myeloproliferative syndromes" by William Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by the selective use of rather mundane, nonspecific therapies that rely on either antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of drug development and discovery for the MPNs after the description of the JAK2 V617F mutation and the role this constitutively active tyrosine kinase has in MPN pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are about to begin) testing for the inhibition of JAK2 in an attempt to improve the treatment of MPNs. Both primary myelofibrosis and myelofibrosis following essential thrombocythemia or polycythemia vera have been the targets of the most extensive testing of these agents to date. Responses to these oral JAK2 inhibitors have been primarily intended to reduce splenomegaly and meaningfully improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are limited. Toxicities have ranged from myelosuppression to significant diarrhea. Additional agents with other mechanisms of action are also targeting JAK2, including histone deacetylase inhibitors and mTOR inhibitors. The results of preliminary trials of JAK2 inhibitors in polycythemia vera and essential thrombocythemia have been mixed but are premature. Many questions remain as to the optimal JAK2 inhibitory strategy and the full extent of the benefit of single-agent JAK2 inhibition.

AB - Ever since their description as "myeloproliferative syndromes" by William Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by the selective use of rather mundane, nonspecific therapies that rely on either antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of drug development and discovery for the MPNs after the description of the JAK2 V617F mutation and the role this constitutively active tyrosine kinase has in MPN pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are about to begin) testing for the inhibition of JAK2 in an attempt to improve the treatment of MPNs. Both primary myelofibrosis and myelofibrosis following essential thrombocythemia or polycythemia vera have been the targets of the most extensive testing of these agents to date. Responses to these oral JAK2 inhibitors have been primarily intended to reduce splenomegaly and meaningfully improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are limited. Toxicities have ranged from myelosuppression to significant diarrhea. Additional agents with other mechanisms of action are also targeting JAK2, including histone deacetylase inhibitors and mTOR inhibitors. The results of preliminary trials of JAK2 inhibitors in polycythemia vera and essential thrombocythemia have been mixed but are premature. Many questions remain as to the optimal JAK2 inhibitory strategy and the full extent of the benefit of single-agent JAK2 inhibition.

KW - Essential thrombocythemia

KW - Jak2 inhibitors

KW - Myelofibrosis

KW - Myeloproliferative neoplasm

KW - Polycythemia vera

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=79551479092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551479092&partnerID=8YFLogxK

U2 - 10.1007/s11899-010-0068-4

DO - 10.1007/s11899-010-0068-4

M3 - Article

C2 - 21080242

AN - SCOPUS:79551479092

VL - 6

SP - 22

EP - 27

JO - Current Hematologic Malignancy Reports

JF - Current Hematologic Malignancy Reports

SN - 1558-8211

IS - 1

ER -