CHRONIC MYELOMONOCYTIC LEUKEMIA - FROM BIOLOGY TO THERAPY

Chronic myelomonocytic leukemia represents a distinct myelodysplastic syndrome in which an excess of monocytes is observed both in the blood and bone marrow of the patients. Whereas diagnosis is relatively easy , therapeutic design and efficacy is difficult and no treatment has to date provided complete or significant partial response. In vitro data suggest that the growth and differentiation of myelomonocytic progeni tors may be altered inasmuch as monocytic or granule-macrophagic colon ies show spontaneous growth. Different entities may be observed: the c hildhood form, Juvenile Chronic Myelomonocytic Leukemia (JCML) shows i n vitro a typical pattern with constitutive growth of only macrophagic colonies and hypersensitivity to GM-CSF; in the adult form at least t wo patterns may be observed one close to the JCML form and one more he terogeneous with absence of GM-CSF sensitivity and spontaneous growth of both CFU-GM and CFU-M colonies. Chemotherapy reduces all myeloid co lonies in vitro whereas retinoic acid has a selective effect on monocy tic colonies with a concomitant increase of CFU-G colonies forwarding an explanation for the correction of pancytopenia observed in some pat ients. Recent analysis of altered molecular pathways in this disease s uggest a common disruption of intracelleular signalling pathways namel y the Ras pathway and targetting for drugs with may selectively contro l or inhibit a constitutive activation may forward novel therapeutic p erspectives.