PMID- 8639795
OWN - NLM
STAT- MEDLINE
DCOM- 19960716
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 87
IP  - 10
DP  - 1996 May 15
TI  - Leukemic burden in subpopulations of CD34+ cells isolated from the mobilized 
      peripheral blood of alpha-interferon-resistant or -intolerant patients with 
      chronic myeloid leukemia.
PG  - 4348-57
AB  - We attempted to determine the frequency of normal hematopoietic stem cells (HSC) 
      and contaminating leukemic cells in mobilized peripheral blood (MPB) collected 
      from chronic myeloid leukemia (CML) patients, intolerant of alpha-interferon or 
      with interferon-resistant disease. A total of 14 MPB samples, six from patients 
      in chronic phase (CP) and eight from patients in accelerated phase or blast 
      crisis (AP/BC) were studied. Cytogenetic analysis of MPB collected from AP/BC 
      patients showed that 100% of the cells were Ph+, whereas cells from four of five 
      CP MPB were Ph-. By contrast, fluorescence in situ hybridization (FISH) analysis 
      of CP MPB showed a mean frequency of 14.7% Ph+ cells, while AP/BC MPB contained 
      39.2% Ph+ cells. In an attempt to purify normal HSC, subpopulations of the MPB 
      CD34+ cells were isolated based on expression of the Thy-1 antigen (CDw90). The 
      mean Ph+ cell frequency as determined by FISH within the CD34+Thy-1+Lin- and 
      CD34+Thy-1-Lin- populations from CP patients was 19.2% and 33.9%, respectively. 
      In the AP/BC patients, levels of residual leukemic cells were significantly 
      greater with mean Ph+ cell frequencies of 59.2% and 72.7% for the CD34+Thy-1+Lin- 
      and CD34+Thy-1-Lin- fractions, respectively. The frequency of cobblestone area 
      forming cells (CAFC) was used as a means of quantitating the numbers of 
      functional HSC within these cell subpopulations. The mean CAFC frequency was 1 of 
      19 for the CD34+Thy-1+Lin- cells as compared with 1 of 133 for the Thy-1-fraction 
      indicating a higher frequency of primitive progenitor cells in the Thy-1+ 
      subpopulation. CD34+ cell subsets from two patients were also injected into 
      SCID-hu bone assays to determine the in vivo behavior of these cell populations. 
      After 8 weeks, multilineage donor engraftment was observed in these grafts. FISH 
      analysis of the donor cells within the grafts showed that 55.3% and 60.0% of the 
      cells were Ph+. We conclude that unfractionated MPB from this patient population 
      is not leukemia-free and that the CD34+Thy-1+Lin- cell subpopulation, although 
      predominantly enriched for normal HSC, still contains substantial numbers of 
      residual leukemic cells.
FAU - Van den Berg, D
AU  - Van den Berg D
AD  - Systemix Inc, Palo Alto, CA, USA.
FAU - Wessman, M
AU  - Wessman M
FAU - Murray, L
AU  - Murray L
FAU - Tong, J
AU  - Tong J
FAU - Chen, B
AU  - Chen B
FAU - Chen, S
AU  - Chen S
FAU - Simonetti, D
AU  - Simonetti D
FAU - King, J
AU  - King J
FAU - Yamasaki, G
AU  - Yamasaki G
FAU - DiGiusto, R
AU  - DiGiusto R
FAU - Gearing, D
AU  - Gearing D
FAU - Reading, C
AU  - Reading C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD34)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interferon-alpha)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - Q20Q21Q62J (Cisplatin)
RN  - UM20QQM95Y (Ifosfamide)
RN  - ICE protocol 1
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antigens, CD34/*analysis
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Blast Crisis/blood/therapy
MH  - *Blood Cell Count
MH  - Bone Transplantation
MH  - Cisplatin/administration & dosage/pharmacology
MH  - Combined Modality Therapy
MH  - Drug Resistance
MH  - Etoposide/administration & dosage/pharmacology
MH  - Fetal Tissue Transplantation
MH  - Flow Cytometry
MH  - Graft Survival
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - *Hematopoietic Stem Cells/chemistry
MH  - Humans
MH  - Ifosfamide/administration & dosage/pharmacology
MH  - Immunologic Factors/*therapeutic use
MH  - *Immunomagnetic Separation
MH  - In Situ Hybridization, Fluorescence
MH  - Interferon-alpha/*therapeutic use
MH  - *Leukapheresis/methods
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*blood/pathology/therapy
MH  - Leukemia, Myeloid, Accelerated Phase/blood/therapy
MH  - Leukemia, Myeloid, Chronic-Phase/blood/therapy
MH  - Mice
MH  - Mice, SCID
MH  - Middle Aged
MH  - Neoplasm Transplantation
MH  - *Neoplastic Cells, Circulating/chemistry
MH  - Philadelphia Chromosome
MH  - Radiation Chimera
MH  - Specific Pathogen-Free Organisms
MH  - Transplantation, Heterologous
EDAT- 1996/05/15 00:00
MHDA- 1996/05/15 00:01
CRDT- 1996/05/15 00:00
PHST- 1996/05/15 00:00 [pubmed]
PHST- 1996/05/15 00:01 [medline]
PHST- 1996/05/15 00:00 [entrez]
AID - S0006-4971(20)63704-1 [pii]
PST - ppublish
SO  - Blood. 1996 May 15;87(10):4348-57.