PMID- 8616015
OWN - NLM
STAT- MEDLINE
DCOM- 19960610
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 92
IP  - 3
DP  - 1996 Mar
TI  - Response of myelodysplastic syndrome marrow progenitor cells to stimualtion with 
      cytokine combinations in a stroma-free long-term culture system.
PG  - 548-58
AB  - The effect of an ex vivo expansion culture system using multiple cytokine 
      combinations was evaluated in 38 cases of myelodysplastic syndrome (MDS) with the 
      aim of overcoming the defective in vitro growth of haemopoietic progenitor cells. 
      A combination of four growth factors (GF) including SCF, IL-3, IL-6 and GM-CSF 
      was identified as the optimal combination for expanding clonogenic progenitor 
      cells in MDS bone marrow liquid cultures. The cultures of 50% of the patients 
      (19/38) responded to GF stimulation (mean CFU-GM fold increase 15.65+/-48 at week 
      4) and showed morphological features of normal and/or dysplastic myeloid 
      differentiation. In 12/38 cases (31%), complete unresponsiveness to multiple 
      cytokine stimulation was observed; a small number of patients (7/38) showed 
      progressive leukaemic growth along the cultures with the presence of 100% 
      immature blasts at week 4. GM-CSF and c-kit receptors, analysed by 
      immuno-histochemistry in 10 patients, were over-expressed in responding patients 
      and either lacking or down-regulated in non-responders. Fluorescence in situ 
      hybridization (FISH) analysis of cultured interphase cells of nine patients 
      (trisomy 8 in eight patients) showed a clear-cut increase in the percentage of 
      cells with three signals in the two responding patients, thus indicating the 
      expansion of a MDS clone. Multiple cytokine liquid cultures seem to be able to 
      override the refractoriness of MDS progenitor cells to GF stimulation in many 
      cases, revealing a heterogeneity which may have prognostic implications and 
      should be considered in ex-vivo and in vivo clinical trials with cytokine 
      combinations.
FAU - Soligo, D A
AU  - Soligo DA
AD  - Bone Marrow Transplantation Unit, Ospedale Maggiore IRCCS, Milan, Italy.
FAU - Campiglio, S
AU  - Campiglio S
FAU - Servida, F
AU  - Servida F
FAU - Bossolasco, P
AU  - Bossolasco P
FAU - Romitti, L
AU  - Romitti L
FAU - Cortelezzi, A
AU  - Cortelezzi A
FAU - Lambertenghi Deliliers, G
AU  - Lambertenghi Deliliers G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Drug Combinations)
RN  - 0 (Interleukin-3)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 0 (Stem Cell Factor)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Bone Marrow/pathology
MH  - Cells, Cultured
MH  - Chromosome Aberrations
MH  - Drug Combinations
MH  - Granulocyte Colony-Stimulating Factor/*pharmacology
MH  - Hematopoietic Stem Cells/drug effects/*pathology
MH  - Humans
MH  - In Situ Hybridization
MH  - Interleukin-3/*pharmacology
MH  - Interleukin-6/*pharmacology
MH  - Karyotyping
MH  - Myelodysplastic Syndromes/*pathology
MH  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Stem Cell Factor/*pharmacology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1046/j.1365-2141.1996.374910.x [doi]
PST - ppublish
SO  - Br J Haematol. 1996 Mar;92(3):548-58. doi: 10.1046/j.1365-2141.1996.374910.x.