Retinoic acid in mono- or combined differentiation therapy of myelodysplasia and acute promyelocytic leukemia.
Myelodysplastic preleukemic syndromes (MDPS) and acute promyelocytic leukemia (APL) share a surprising in vivo sensitivity to the hormonally acting 13 cis or all trans retinoic acids (transRA). Here we show that transRA as a monotherapeutic agent induced a stable remission in APL at the third relapse. In MDPS, treatment with prednisone and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25D3) 13 cis RA induced a long-lasting hematological remission. Initially both patients had an impaired BM microenvironment which regenerated on retinoid therapy as judged by reappearance of the Hematon fraction in the BM aspirates. Our preclinical experiments using long-term liquid BM cultures (LTBMC) indicated that several individual patterns of growth and differentiation responses can be induced by combinations of transRA, 1 alpha,25D3 and hemopoietic growth factors (HGFs). The biological responses may vary from complete clonal extinction to a significant growth stimulation of the leukemic blast cell populations. These results further support the importance of preclinical studies in selecting "good" responders for, and excluding "poor" responders from protocols using differentiation therapy.
ICIG, Association Claude Bernard, Hôpital Paul Brousse, Villejuif, France.
I
I
Blazsek
C
C
Farabos
M
M
Musset
E
E
Goldschmidt
M
M
Comisso
M
M
Benavides
Z Y
ZY
Wang
M L
ML
Labat
G
G
Mathé
J L
JL
Misset
D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D014212:Tretinoin; D002117:Calcitriol; D011241:Prednisone