The constitutive mobilization of bone marrow-repopulating cells into the peripheral blood in idiopathic myelofibrosis.
Idiopathic myelofibrosis (IM) is characterized by the constitutive mobilization of CD34(+) cells. IM peripheral blood (PB) CD34(+) cells had a reduced cloning efficiency and a lower frequency of cobblestone areas compared with normal granulocyte colony-stimulating factor (G-CSF)-mobilized PB CD34(+) cells. IM CD34(+) cells engrafted nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, demonstrating that they contain bone marrow (BM)-repopulating cells. G-CSF-mobilized CD34(+) cells produced multiple hematopoietic lineages within the NOD/SCID mice with a predominance of CD19(+) cells. By contrast, IM CD34(+) cells produced predominantly CD33(+) cells, increased numbers of CD41(+) cells, but fewer CD19(+) cells. Transcriptional clonality assays of the engrafted human IM cells demonstrated their clonal origin. CD34(+) cells from one patient isolated prior to leukemic transformation were capable of generating acute leukemia in NOD/SCID mice. The engrafted human cells exhibited the same abnormal karyotype as primary cells in a portion of the population. These findings demonstrate that BM-repopulating cells and more differentiated progenitor cells are constitutively mobilized into the PB in IM, and that their differentiation program is abnormal. In addition, the NOD/SCID model may be useful in gaining an understanding of the events occurring during the transition of IM to acute leukemia.
Section of Hematology/Oncology, University of Illinois at Chicago Cancer Center, Chicago, IL 60607-7171, USA.
Mingjiang
M
Xu
Edward
E
Bruno
Joseph
J
Chao
Hongyu
H
Ni
Valerie
V
Lindgren
Rafael
R
Nunez
Nadim
N
Mahmud
Guido
G
Finazzi
Steven M
SM
Fruchtman
Uday
U
Popat
Enli
E
Liu
Josef T
JT
Prchal
Damiano
D
Rondelli
Giovanni
G
Barosi
Ronald
R
Hoffman
D000208:Acute Disease; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement; D002999:Clone Cells; D005260:Female; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055728:Primary Myelofibrosis / Q000097:blood* / Q000235:genetics / Q000473:pathology*
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor