Ten human kidney specimens and thirty-two renal cell carcinomas were investigated for the presence of transthyretin mRNA and cystatin C mRNA using Northern blot analysis. Five of ten kidney specimens and 15 of 32 renal carcinomas were also immunohistochemically investigated for the presence of the corresponding proteins. Transthyretin mRNA could not be detected in any of the normal or neoplastic tissue preparations, whereas low amounts of cystatin C mRNA were found in nine of ten normal kidneys and in 24 of 32 renal cell carcinomas. Immunoreactive transthyretin and cystatin C were present in proximal tubular epithelial cells of all kidney specimens, whereas neither of the proteins was detected the tumour cells of the renal carcinomas. Immunoreactive cystatin C was, however, demonstrated in scattered monocyte/macrophage-like cells. We conclude that the presence of immunoreactive transthyretin and cystatin C in proximal tubular cells of the kidney is most likely due to reabsorption of the proteins from the primary urine. The small amounts of cystatin C mRNA in some of the normal and neoplastic renal preparations are probably due to cystatin C synthesis in macrophages. Transthyretin has been recommended as an immunohistochemical marker for renal cell carcinomas. Our results, however, clearly indicate that neither transthyretin nor cystatin C constitutes a useful marker for such neoplasms.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q− syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q−), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q− syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34+CD38− HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34+CD19+ pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34+CD38−, but inefficient at reconstituting hematopoiesis.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q− syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q−), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q− syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34+CD38− HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34+CD19+ pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34+CD38−, but inefficient at reconstituting hematopoiesis.