All trans retinoic acid abrogates spontaneous monocytic growth in juvenile chronic myelomonocytic leukaemia.
BACKGROUND
All trans retinoic acid, the active metabolite of vitamin A, exerts profound effects on cell differentiation. On normal myeloid progenitors, retinoids switch the differentiation program of granulo-macrophagic progenitors towards the granulocytic lineage and consequently reduce CFU-M colony formation. Bone marrow and peripheral blood mononuclear cells from children with Juvenile Chronic Myelomonocytic Leukaemia show typical spontaneous monocytic growth. We questioned whether in this disease, retinoids could switch myelomonocytic growth and inhibit the abnormal CFU-M colony proliferation.


METHODS
Ten JCML samples were studied in the presence of ATRA in methyl cellulose colony assay, before (CFU-C) or after (pre-CFU) liquid suspension culture.


RESULTS
In vitro characteristics of JCML such as spontaneous monocytic growth in the absence of growth factor was noted in all patients. In the presence of leucocyte-conditioned medium, nine samples showed only CFU-M growth and one sample CFU-GM growth. Incubation with ATRA inhibited CFU-M colony formation in nine cases. Enhancement of granulocytic differentiation (CFU-G) was noted in nine cases. ATRA also inhibited CD34+ JCML monocytic growth and GM-CSF hypersensitivity.


CONCLUSIONS
These data suggest that, in JCML progenitors, retinoid pathways are functional and inhibition of immature monocytic progenitors cells may be achieved with retinoids, without impeding granulocytic cell growth.
Cambier
N
N
LBCH (laboratoire de Biologie Cellulaire Hématopoïétique) Service de Médecine Nucléaire, INSERM E00-03, Hôpital Saint Louis, 1 avenue Claude Vellefaux, Paris 75475, Paris cédex 10, France.
Menot
M L
ML
Schlageter
M H
MH
Balitrand
N
N
Leblanc
T
T
Bordigoni
P
P
Rohrlich
P
P
Lamagnère
J P
JP
Donadieu
J
J
Herbelin
C
C
Puissant
C
C
Gourand
F
F
Baruchel
A
A
Chomienne
C
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D005260:Female; D042381:Granulocyte Precursor Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014212:Tretinoin