Prognostic value of c-mpl expression in myelodysplastic syndromes.
The c-mpl proto-oncogene which encodes a member of the hematopoietic cytokine receptor superfamily has been recently shown to be the receptor for thrombopoietin (TPO), which stimulates megakaryocyte progenitor expansion and differentiation. We studied c-mpl expression by Northern blot analysis, in a large series of 58 MDS. No expression was found in 14 patients with refractory anemia (RA) or with refractory anemia with ring sideroblasts (RARS). In contrast 11/26 (42%) patients with refractory anemia with excess of blasts (RAEB), or with RAEB in transformation (RAEBt), and 8/18 (44%) patients with chronic myelomonocytic leukemia (CMML) expressed c-mpl. In CMML patients, no correlation was found between c-mpl expression and any prognostic factor tested, nor with the course of the disease. In contrast, in RAEB and RAEBt, expression of c-mpl was correlated with high Bournemouth scoring (P < 0.005) and poor survival (P = 0.02) due to leukemic transformation. Forty-five per cent (5/11) of the c-mpl positive patients evolved towards AML with a mean follow-up of 10.5 months, while 13% (2/15) of the c-mpl negative patients developed a secondary leukemia, with a mean follow-up of 21.1 months. Moreover, in RAEB and RAEBt, a significant correlation was observed between c-mpl, CD34, megakaryocyte glycoprotein IIb (GPIIb) expression, and the presence of dysmegakaryopoiesis. These results indicate that patients with RAEB and RAEBt, with high expression of the c-mpl, CD34, and GPIIb genes, may identify a subgroup of patients with particularly poor prognosis, due to an increased risk of secondary leukemia. More aggressive therapy could be justified in these patients.
Bouscary
D
D
Hematology Department, Hôpital Cochin, Paris, France.
Preudhomme
C
C
Ribrag
V
V
Melle
J
J
Viguié
F
F
Picard
F
F
Guesnu
M
M
Fenaux
P
P
Gisselbrecht
S
S
Dreyfus
F
F
D015703:Antigens, CD / Q000235:genetics; D018952:Antigens, CD34; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D053628:Receptors, Thrombopoietin; D012189:Retrospective Studies
D015703:Antigens, CD; D018952:Antigens, CD34; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human