Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients.

Cytogenetic stratification remains insufficient for almost half of the acute myeloblastic leukemia (AML) cases, with AML patients requiring subsequent molecular investigation. In our study, we used mass spectrometry (MS)-based proteomic approaches to characterize de novo AML. Fifty-four samples (mononuclear cells from bone marrow or peripheral blood mononuclear cells collected and frozen before treatment) from two independent cohorts of newly diagnosed AML patients were analyzed. We showed that the protein signature of leukemic cells defined two clusters that displayed significant variation for overall and disease-free survival (P=0.001 and 0.0004, respectively). This proteomic classification refines the cytogenetic classes. AML patients with intermediate and unfavorable cytogenetic classifications could be subdivided according to their protein profiles into subgroups with significantly different survival rates. Among the proteins expressed by leukemic cells, we isolated a 10,800-Da marker that retained the highest discriminative value between living and deceased patients. The 10,800-Da marker was identified by MS peptide sequencing as S100A8 (also designated MRP8 or calgranulin A). Western blot analysis confirmed its expression mainly in AML patients with the worst prognosis, arguing for a selective deregulation associated with poor prognosis. These results suggest that the expression of S100A8 in leukemic cells is a predictor of low survival.

The cord blood oxygen affinity from normal human newborns: 1) A methodological approach.

A correct analysis of O2 affinity in neonatal whole blood puts some important, still unsolved problems of methodology, mainly based upon the fact that this kind of blood is a mixture of at least two major hemoglobins, i.e. 2/3 Hb-F and 1/3 Hb-A, having different affinities. Whereas adult blood mainly contains Hb-A. Within such a perspective, the Authors have checked if the empirical Davenport's nomogram, correcting the pO2s of adult blood to the same standard pH of 7.4, can also be used for neonatal blood. The answer is affirmative, and in addition the nomogram can also be replaced, with some advantage, by an only mathematical correction of the measured pO2s, in which pH differences from 7.4 (either positive or negative) are converted in proportional differences of pO2 and either added or subtracted to the values of these latter. Hb-CO level is undoubtedly higher in newborns than in non-smoker adults, but no factor for T50 calculation of neonatal blood has been till now identified. The Authors have determined a factor of -0.36, which can be obtained from the homologous (experimental) "adult" factor of -0.27, by multiplying this latter for 1.35.