Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.
To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.
Hanania
E G
EG
University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Giles
R E
RE
Kavanagh
J
J
Fu
S Q
SQ
Ellerson
D
D
Zu
Z
Z
Wang
T
T
Su
Y
Y
Kudelka
A
A
Rahman
Z
Z
Holmes
F
F
Hortobagyi
G
G
Claxton
D
D
Bachier
C
C
Thall
P
P
Cheng
S
S
Hester
J
J
Ostrove
J M
JM
Bird
R E
RE
Chang
A
A
Korbling
M
M
Seong
D
D
Cote
R
R
Holzmayer
T
T
Deisseroth
A B
AB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D017931:DNA Primers; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016133:Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D005047:Etoposide; D003520:Cyclophosphamide