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Six Algerian patients with ß0 thalassemia are presented, in addition to the two patients already reported (Godet et al., 1977). Family studies indicate that all the patients had homozygous ß thalassemia characterized by absence of ß globin chain synthesis in peripheral blood. The clinical severity varies from one family to the other and within the same family, from typical Cooley's anemia to thalassemia intermedia and appears to be related to the child death rate observed in each family. The ?/a biosynthetic ratio was 0.36–0.40 in seven patients and 0.2 in the most seriously affected patient. The mRNAß content in peripheral reticulocytes was less than 1.5% of mRNAa in seven patients and 13.3% in one patient. These results indicate that Algerians homozygous for ß thalassemia are heterozygous at the clinical, biochemical and molecular levels.

NFS-60 and FDCP-Mix cells are interleukin-3–dependent multipotent hematopoietic cells that can differentiate in vitro into mature myeloid and erythroid cells. Retrovirus-mediated transfer of the human colony-stimulating factor-1 (CSF-1) receptor gene (c-fms) enabled NFS-60 cells but not FDCP-Mix cells to proliferate in response to CSF-1. The phenotype of NFS-60 cells expressing the human CSF-1 receptor (CSF-1R) grown in CSF-1 did not grossly differ from that of original NFS-60 as assessed by cytochemical and surface markers. Importantly, these cells retained their erythroid potentiality. In contrast, a CSF-1–dependent variant of NFS-60, strongly expressing murine CSF-1 R, differentiated into monocyte/macrophages upon CSF-1 stimulation and almost totally lost its erythroid potentiality. We also observed that NFS-60 but not FDCP-Mix cells could grow in response to stem cell factor, (SCF), although both cell lines express relatively high amounts of SCF receptors. This suggests that SCF-R and CSF-1 R signalling pathways share at least one component that may be missing or insufficiently expressed in FDCP-Mix cells. Taken together, these results suggest that human CSF-1 R can use the SCF-R signalling pathway in murine multipotent cells and thereby favor self-renewal versus differentiation.

An atypical sickle cell trait with a very low level of hemoglobin S and features of heterozygous β-thalassemia was recently described. In vitro globin chain synthesis strongly suggested the presence of the two abnormalities on the same chromosome. We report the corresponding βs-thalgene. DNA sequence revealed a C → T base substitu tion in the distal promoter element CACCC, at position – 88 from the cap site, in addition to the expected GAG → GTG mutation responsible for the structural vari ant [β6 Glu → Val). Reticulocyte mRNA titration and transient assay of the mutant gene in COS cells showed a defect in β-mRNA production. Restriction haplotype and

We previously hypothesized that a 2 nucleotide deletion, causing a A→C change at position –3 preceeding the ATG initiation codon of o globin gene, reduced translation efficiency of aglobin mRNA and was responsible for a form of α+ thalassemia displayed by an Algerian patient (1,2). We presently show that this deletion leads to a 30–45% reduction in translation efficiency of synthetic aglobin mRNA in rabbit reticulocyte lysate. In other experiments, we constructed α/G yhybrid globin genes in which the 3'end of normal or mutated aglobin genes downstream to the ATG initiation codon was substituted by the 3' part of a Gy globin gene. C05 cells transfected with either of these 2 hybrid genes were shown to synthesize a similar amount of α/G y hybrid mRNAs but 50% less Gy globin when transfected with the α/GY hybrid gene carrying the deletion. These results definitively establish that the 2 nucleotide deletion reduces translation efficiency by 30–5058. This contrasts with the 93% reduction induced by a similar A→C change at position –3 in the different nucleotide context preceeding the ATG codon of the rat preproinsulin gene (3).