The role of PML in hematopoietic and leukemic stem cell maintenance

Fumio Nakahara, Cary N. Weiss, Keisuke Ito

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The tumor suppressor promyelocytic leukemia (PML) was first identified as a component of PML-RARα fusion protein, one of the initiating cytogenetic abnormalities in acute promyelocytic leukemia. PML is now known to have diverse functions regulating the DNA-damage response, apoptosis, senescence, and angiogenesis. Recent investigations have identified PML as a regulator of metabolic pathways in stem cell compartments, including the hematopoietic system, and have provided researchers with new strategies for controlling stem cell maintenance and differentiation. Studies of PML in leukemia-initiating cells demonstrate that PML is also an essential component of their maintenance, which has drawn tremendous attention to PML from scientists in various stem cell fields. Here, we review research into PML and its associated pathways, including recent studies of PML as it relates to stem cell biology, as well as our finding that PML regulates fatty acid oxidation, which is essential to the maintenance of normal hematopoietic stem cells. We also discuss the therapeutic potential of controlling PML-associated pathways. In particular, we describe promising evidence for the use of arsenic trioxide in the treatment of chronic myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)18-26
Number of pages9
JournalInternational Journal of Hematology
Volume100
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Hematopoietic Stem Cells
Leukemia
Maintenance
Stem Cells
Hematopoietic System
Acute Promyelocytic Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Metabolic Networks and Pathways
Chromosome Aberrations
DNA Damage
Cell Biology
Cell Differentiation
Fatty Acids
Research Personnel
Apoptosis

Keywords

  • Hematopoietic stem cells
  • Leukemia stem cells
  • PML
  • Stem cell metabolism

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

The role of PML in hematopoietic and leukemic stem cell maintenance. / Nakahara, Fumio; Weiss, Cary N.; Ito, Keisuke.

In: International Journal of Hematology, Vol. 100, No. 1, 2014, p. 18-26.

Research output: Contribution to journalArticle

Nakahara, Fumio ; Weiss, Cary N. ; Ito, Keisuke. / The role of PML in hematopoietic and leukemic stem cell maintenance. In: International Journal of Hematology. 2014 ; Vol. 100, No. 1. pp. 18-26.
@article{c717c2d28da248d5acfca5855db4c77c,
title = "The role of PML in hematopoietic and leukemic stem cell maintenance",
abstract = "The tumor suppressor promyelocytic leukemia (PML) was first identified as a component of PML-RARα fusion protein, one of the initiating cytogenetic abnormalities in acute promyelocytic leukemia. PML is now known to have diverse functions regulating the DNA-damage response, apoptosis, senescence, and angiogenesis. Recent investigations have identified PML as a regulator of metabolic pathways in stem cell compartments, including the hematopoietic system, and have provided researchers with new strategies for controlling stem cell maintenance and differentiation. Studies of PML in leukemia-initiating cells demonstrate that PML is also an essential component of their maintenance, which has drawn tremendous attention to PML from scientists in various stem cell fields. Here, we review research into PML and its associated pathways, including recent studies of PML as it relates to stem cell biology, as well as our finding that PML regulates fatty acid oxidation, which is essential to the maintenance of normal hematopoietic stem cells. We also discuss the therapeutic potential of controlling PML-associated pathways. In particular, we describe promising evidence for the use of arsenic trioxide in the treatment of chronic myeloid leukemia.",
keywords = "Hematopoietic stem cells, Leukemia stem cells, PML, Stem cell metabolism",
author = "Fumio Nakahara and Weiss, {Cary N.} and Keisuke Ito",
year = "2014",
doi = "10.1007/s12185-014-1518-x",
language = "English (US)",
volume = "100",
pages = "18--26",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "1",

}

TY - JOUR

T1 - The role of PML in hematopoietic and leukemic stem cell maintenance

AU - Nakahara, Fumio

AU - Weiss, Cary N.

AU - Ito, Keisuke

PY - 2014

Y1 - 2014

N2 - The tumor suppressor promyelocytic leukemia (PML) was first identified as a component of PML-RARα fusion protein, one of the initiating cytogenetic abnormalities in acute promyelocytic leukemia. PML is now known to have diverse functions regulating the DNA-damage response, apoptosis, senescence, and angiogenesis. Recent investigations have identified PML as a regulator of metabolic pathways in stem cell compartments, including the hematopoietic system, and have provided researchers with new strategies for controlling stem cell maintenance and differentiation. Studies of PML in leukemia-initiating cells demonstrate that PML is also an essential component of their maintenance, which has drawn tremendous attention to PML from scientists in various stem cell fields. Here, we review research into PML and its associated pathways, including recent studies of PML as it relates to stem cell biology, as well as our finding that PML regulates fatty acid oxidation, which is essential to the maintenance of normal hematopoietic stem cells. We also discuss the therapeutic potential of controlling PML-associated pathways. In particular, we describe promising evidence for the use of arsenic trioxide in the treatment of chronic myeloid leukemia.

AB - The tumor suppressor promyelocytic leukemia (PML) was first identified as a component of PML-RARα fusion protein, one of the initiating cytogenetic abnormalities in acute promyelocytic leukemia. PML is now known to have diverse functions regulating the DNA-damage response, apoptosis, senescence, and angiogenesis. Recent investigations have identified PML as a regulator of metabolic pathways in stem cell compartments, including the hematopoietic system, and have provided researchers with new strategies for controlling stem cell maintenance and differentiation. Studies of PML in leukemia-initiating cells demonstrate that PML is also an essential component of their maintenance, which has drawn tremendous attention to PML from scientists in various stem cell fields. Here, we review research into PML and its associated pathways, including recent studies of PML as it relates to stem cell biology, as well as our finding that PML regulates fatty acid oxidation, which is essential to the maintenance of normal hematopoietic stem cells. We also discuss the therapeutic potential of controlling PML-associated pathways. In particular, we describe promising evidence for the use of arsenic trioxide in the treatment of chronic myeloid leukemia.

KW - Hematopoietic stem cells

KW - Leukemia stem cells

KW - PML

KW - Stem cell metabolism

UR - http://www.scopus.com/inward/record.url?scp=84904317280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904317280&partnerID=8YFLogxK

U2 - 10.1007/s12185-014-1518-x

DO - 10.1007/s12185-014-1518-x

M3 - Article

C2 - 24488785

AN - SCOPUS:84904317280

VL - 100

SP - 18

EP - 26

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

IS - 1

ER -