The chemokine CCL21 protects normal marrow progenitors from ara-C cytotoxicity

Robert Hromas, Scott Cooper, Hal E. Broxmeyer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Chemokines are a family of small proteins that regulate leukocyte infiltration into inflamed tissue and play key roles in the pathogenesis of many diseases. Some chemokines can also reversibly inhibit the proliferation of hematopoietic progenitors. We have previously found that the chemokine CCL21 (Exodus-2/SLC/6Ckine/TCA4) is a potent inhibitor of the proliferation of normal hematopoietic progenitors. In this study we sought to determine whether this inhibition of proliferation could be therapeutically exploited by protecting normal marrow progenitors from the cytotoxicity of the S phase-active chemotherapeutic agent Ara-C. Methods: Untreated and CCL21-pretreated mice were given doses of Ara-C that are toxic to marrow myeloid progenitors. The recovery of these myeloid progenitors was analyzed by colony formation assays. Results: It was found that pretreatment with small doses of CCL21 prevented the death of normal murine marrow progenitors from the toxic effects of Ara-C. Conclusions: The chemokine CCL21 may be able to prevent Ara-C myelosuppression during acute leukemia induction chemotherapy, and thereby decrease morbidity and mortality of such therapy, and shorten hospital stays.

Original languageEnglish (US)
Pages (from-to)163-166
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume50
Issue number2
DOIs
StatePublished - Sep 12 2002

Fingerprint

Chemokine CCL21
Cytarabine
Cytotoxicity
Bone Marrow
Poisons
Chemokines
Induction Chemotherapy
Chemotherapy
S Phase
Infiltration
Assays
Length of Stay
Leukemia
Leukocytes
Tissue
Morbidity
Recovery
Mortality
Proteins

Keywords

  • Ara-C
  • Chemokine
  • Leukemia
  • Myeloid progenitors
  • Myelosuppression

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

The chemokine CCL21 protects normal marrow progenitors from ara-C cytotoxicity. / Hromas, Robert; Cooper, Scott; Broxmeyer, Hal E.

In: Cancer Chemotherapy and Pharmacology, Vol. 50, No. 2, 12.09.2002, p. 163-166.

Research output: Contribution to journalArticle

@article{eb3b5a830fd644aa82d3054792a994d6,
title = "The chemokine CCL21 protects normal marrow progenitors from ara-C cytotoxicity",
abstract = "Purpose: Chemokines are a family of small proteins that regulate leukocyte infiltration into inflamed tissue and play key roles in the pathogenesis of many diseases. Some chemokines can also reversibly inhibit the proliferation of hematopoietic progenitors. We have previously found that the chemokine CCL21 (Exodus-2/SLC/6Ckine/TCA4) is a potent inhibitor of the proliferation of normal hematopoietic progenitors. In this study we sought to determine whether this inhibition of proliferation could be therapeutically exploited by protecting normal marrow progenitors from the cytotoxicity of the S phase-active chemotherapeutic agent Ara-C. Methods: Untreated and CCL21-pretreated mice were given doses of Ara-C that are toxic to marrow myeloid progenitors. The recovery of these myeloid progenitors was analyzed by colony formation assays. Results: It was found that pretreatment with small doses of CCL21 prevented the death of normal murine marrow progenitors from the toxic effects of Ara-C. Conclusions: The chemokine CCL21 may be able to prevent Ara-C myelosuppression during acute leukemia induction chemotherapy, and thereby decrease morbidity and mortality of such therapy, and shorten hospital stays.",
keywords = "Ara-C, Chemokine, Leukemia, Myeloid progenitors, Myelosuppression",
author = "Robert Hromas and Scott Cooper and Broxmeyer, {Hal E.}",
year = "2002",
month = "9",
day = "12",
doi = "10.1007/s00280-002-0486-7",
language = "English (US)",
volume = "50",
pages = "163--166",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - The chemokine CCL21 protects normal marrow progenitors from ara-C cytotoxicity

AU - Hromas, Robert

AU - Cooper, Scott

AU - Broxmeyer, Hal E.

PY - 2002/9/12

Y1 - 2002/9/12

N2 - Purpose: Chemokines are a family of small proteins that regulate leukocyte infiltration into inflamed tissue and play key roles in the pathogenesis of many diseases. Some chemokines can also reversibly inhibit the proliferation of hematopoietic progenitors. We have previously found that the chemokine CCL21 (Exodus-2/SLC/6Ckine/TCA4) is a potent inhibitor of the proliferation of normal hematopoietic progenitors. In this study we sought to determine whether this inhibition of proliferation could be therapeutically exploited by protecting normal marrow progenitors from the cytotoxicity of the S phase-active chemotherapeutic agent Ara-C. Methods: Untreated and CCL21-pretreated mice were given doses of Ara-C that are toxic to marrow myeloid progenitors. The recovery of these myeloid progenitors was analyzed by colony formation assays. Results: It was found that pretreatment with small doses of CCL21 prevented the death of normal murine marrow progenitors from the toxic effects of Ara-C. Conclusions: The chemokine CCL21 may be able to prevent Ara-C myelosuppression during acute leukemia induction chemotherapy, and thereby decrease morbidity and mortality of such therapy, and shorten hospital stays.

AB - Purpose: Chemokines are a family of small proteins that regulate leukocyte infiltration into inflamed tissue and play key roles in the pathogenesis of many diseases. Some chemokines can also reversibly inhibit the proliferation of hematopoietic progenitors. We have previously found that the chemokine CCL21 (Exodus-2/SLC/6Ckine/TCA4) is a potent inhibitor of the proliferation of normal hematopoietic progenitors. In this study we sought to determine whether this inhibition of proliferation could be therapeutically exploited by protecting normal marrow progenitors from the cytotoxicity of the S phase-active chemotherapeutic agent Ara-C. Methods: Untreated and CCL21-pretreated mice were given doses of Ara-C that are toxic to marrow myeloid progenitors. The recovery of these myeloid progenitors was analyzed by colony formation assays. Results: It was found that pretreatment with small doses of CCL21 prevented the death of normal murine marrow progenitors from the toxic effects of Ara-C. Conclusions: The chemokine CCL21 may be able to prevent Ara-C myelosuppression during acute leukemia induction chemotherapy, and thereby decrease morbidity and mortality of such therapy, and shorten hospital stays.

KW - Ara-C

KW - Chemokine

KW - Leukemia

KW - Myeloid progenitors

KW - Myelosuppression

UR - http://www.scopus.com/inward/record.url?scp=0036351301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036351301&partnerID=8YFLogxK

U2 - 10.1007/s00280-002-0486-7

DO - 10.1007/s00280-002-0486-7

M3 - Article

C2 - 12172984

AN - SCOPUS:0036351301

VL - 50

SP - 163

EP - 166

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -