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In eight cases of extended tumors of oral cavity, we have studied the growth rate, the cell kinetics parameters, and the histology before and during treatment. We have found that growth rate and cell kinetics are not useful for clinical purposes because the first is not related to the response to treatment, while the second is unable to give relevant parameters in solid human tumors. New information was obtained from examination of serial biopsies before and throughout the treatment. These data suggest that multiple subpopulation groups of cancer cells with different intrinsic sensitivity to chemotherapy and/or radiotherapy may exist in the same tumor. Resistance of the tumor is related to some groups of cells scarcely sensitive to treatment.

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Cab4b, the first human platelet antigen carried by glycoprotein IX discovered in a context of severe neonatal thrombocytopenia V . J A L L U , T. BERANGER, F. BIANCHI, C. CASALE, C. CHE N E T , N . F E R R E , S . P H I L I P P E , J . Q U E S N E , C . M A R T A G E I X and R . P E T E R M A N N Essentials• Life-threatening maternofetal thrombocytopenias mostly depend on a IIb b 3 antigens.• We performed serological, genomic and in vitro studies of two life-threatening thrombocytopenias.• Identification of a c.368C>T variation leading to Pro123Leu substitution in GPIX.• A rare GPIX variant reported in a genomic database define a new alloantigen.Summary. Background: After three miscarriages, a 39-yearold woman gave birth, with a 1-year interval, to two severely thrombocytopenic neonates (4 910 9 L -1 and 33 910 9 L -1 ) with intracranial hemorrhages. Transfusion of platelet concentrates corrected the thrombocytopenia. The outcome was favorable for the first child, but the second one died 10 days after cesarean delivery (31 weeks of gestation + 6 days). Methods: Serologic studies were performed with mAb-specific immobilization of platelet antigens and flow cytometry techniques. Human platelet alloantigen (HPA) genotyping was performed with the BioArray HPA BeadChip and PCR-sequence-specific primer techniques. Genomic DNA was studied by direct sequencing of PCR products. The mutant glycoprotein (GP) was expressed in transiently transfected HEK293 cells. Results: In MAIPA assay, the maternal serum faintly reacted with GPIbIX from paternal and child 1 platelets, but not with maternal or panel platelets. No maternofetal incompatibility was found in the 22 known HPA systems, tested except for HPA-1b in child 2. A new alloantigen carried by GPIbIX was suspected. Genomic sequencing revealed a paternal GPIX variation (NM_000174.4: c.368C>T). The father and children were heterozygous and incompatible with the mother, who was NM_000174.4: c.368C homozygous. The maternal serum reacted with the GPIX NP_000165.1:p.Leu123 form coexpressed with GPIb in transfected HEK293 cells. The NM_000174.4:c.368T allele (rs202229101) has a minor allele frequency of 0.0002, and was not detected in 120 French subjects (families with fetal and neonatal alloimmune thrombocytopenia [FNAIT]), suggesting that it is rarely implicated in alloimmunization. Conclusion: The NP_000165.1:p.Leu123 allele named Cab4b is the first platelet alloantigen described on GPIX. In the absence of other known maternofetal incompatibility, the child 1 case suggests that anti-Cab4b alloantibodies can induce severe thrombocytopenias.