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A critical issue for clinical utilization of human ES cells (hESCs) is whether they can generate terminally mature progenies with normal function. We recently developed a method for efficient production of hematopoietic progenitors from hESCs by coculture with murine fetal liver-derived stromal cells. Large numbers of hESCs-derived erythroid progenitors generated by the coculture enabled us to analyze the development of erythropoiesis at a clone level and investigate their function. The results showed that the globin expression in the erythroid cells in individual clones changed in a time-dependent manner. In particular, embryonic ε-globin-expressing erythroid cells from individual clones decreased, whereas adult-type β-globin-expressing cells increased to ≈100% in all clones we examined, indicating that the cells undergo definitive hematopoiesis. Enucleated erythrocytes also appeared among the clonal progeny. A comparison analysis showed that hESC-derived erythroid cells took a similar differentiation pathway to human cord blood CD34+ progenitor-derived cells when examined for the expression of glycophorin A, CD71 and CD81. Furthermore, these hESC-derived erythroid cells could function as oxygen carriers and had a sufficient glucose-6-phosphate dehydrogenase activity. The present study should provide an experimental model for exploring early development of human erythropoiesis and hemoglobin switching and may help in the discovery of drugs for hereditary diseases in erythrocyte development [ABSTRACT FROM AUTHOR]

Juvenile myelomonocytic leukemia (JMML) is a myelodysplastic/myeloproliferative disorder of young children. Because the disease is rare and the diagnosis is difficult, a prospective registration of patients suspected of having JMML with a pathological central review have been conducted by the MDS Committee of the Japanese Society of Pediatric Hematology. Between 1999 and 2006, 75 children with JMML were enrolled and diagnosed through this system. Median age at diagnosis was 20 months (1∼85 months). Cytogenetic abnormalities were detected in 21 patients, including 11 with monosomy 7. The 5-year overall survival (OS) was 60%. Regarding the treatment, 61 of the 75 patients received stem cell transplantation (SCT). Conditioning regimen varied widely, and the source of grafts was bone marrow for 43 patients, peripheral blood for 5, and cord blood for 13. The 5-year OS after SCT was 61%. Notably, patients who received cord blood transplantation had inferior survival than those who received grafts from other sources (38 vs. 68%; P=0.03). Given better recognition of the disease, a multi-center protocol study on SCT, JMML11, is now being planned by the Japanese Pediatric Leukemia/Lymphoma Study Group.

The morphological discrimination of leukemic from non-leukemic T cells is often difficult in adult T-cell leukemia (ATL) as ATL cells show morphological diversity, with the exception of typical "flower cells." Because defects in the expression of CD3 as well as CD7 are common in ATL cells, we applied multi-color flow cytometry to detect a putative leukemia-specific cell population in the peripheral blood from ATL patients. CD4(+) CD14(-) cells subjected to two-color analysis based on a CD3 vs CD7 plot clearly demonstrated the presence of a CD3(dim) CD7(low) subpopulation in each of nine patients with acute-type ATL. The majority of sorted cells from this fraction showed a flower cell-like morphology and carried a high proviral load for the human T-cell leukemia virus type 1 (HTLV-I). Genomic integration site analysis (inverse long-range PCR) and analysis of the T cell receptor Vβ repertoire by flow cytometry indicated that the majority of leukemia cells were included in the CD3(dim) CD7(low) subpopulation. These results suggest that leukemic T cells are specifically enriched in a unique CD3(dim) CD7(low) subpopulation of CD4(+) T cells in acute-type ATL., (© 2011 Japanese Cancer Association.)