Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.
Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet production. Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteristic of myeloproliferative leukemia (MPL) viral disease led us to investigate whether this receptor-ligand system may play a role in erythropoiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy with erythropoietin to expand these populations. Moreover, while the effects on erythropoiesis in normal animals were modest, TPO greatly expanded the number of erythroid progenitors and blood reticulocytes and was associated with accelerated red cell recovery in myelosuppressed mice. Together, these data strongly suggest that erythroid progenitors respond to TOP and that this newly cloned cytokine, critical for platelet production, can augment erythropoiesis in states of marrow failure.
Kaushansky
K
K
Division of Hematology, University of Washington, Seattle 98195, USA.
Broudy
V C
VC
Grossmann
A
A
Humes
J
J
Lin
N
N
Ren
H P
HP
Bailey
M C
MC
Papayannopoulou
T
T
Forstrom
J W
JW
Sprugel
K H
KH
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D016190:Carboplatin / Q000633:toxicity*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011519:Proto-Oncogenes; D018121:Receptors, Cytokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013926:Thrombopoietin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014916:Whole-Body Irradiation
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; D016190:Carboplatin