Purpose: Cell adhesion molecule 1 (CADM1), initially identified as a tumor suppressor gene, has recently been reported to be ectopically expressed in primary adult T-cell leukemia–lymphoma (ATL) cells. We incorporated CADM1 into flow-cytometric analysis to reveal oncogenic mechanisms in human T-cell lymphotrophic virus type I (HTLV-I) infection by purifying cells from the intermediate stages of ATL development. Experimental Design: We isolated CADM1- and CD7-expressing peripheral blood mononuclear cells of asymptomatic carriers and ATLs using multicolor flow cytometry. Fluorescence-activated cell sorted (FACS) subpopulations were subjected to clonal expansion and gene expression analysis. Results: HTLV-I–infected cells were efficiently enriched in CADM1+ subpopulations (D, CADM1posCD7dim and N, CADM1posCD7neg). Clonally expanding cells were detected exclusively in these subpopulations in asymptomatic carriers with high proviral load, suggesting that the appearance of D and N could be a surrogate marker of progression from asymptomatic carrier to early ATL. Further disease progression was accompanied by an increase in N with a reciprocal decrease in D, indicating clonal evolution from D to N. The gene expression profiles of D and N in asymptomatic carriers showed similarities to those of indolent ATLs, suggesting that these subpopulations represent premalignant cells. This is further supported by the molecular hallmarks of ATL, that is, drastic downregulation of miR-31 and upregulation of abnormal Helios transcripts. Conclusion: The CADM1 versus CD7 plot accurately reflects disease progression in HTLV-I infection, and CADM1+ cells with downregulated CD7 in asymptomatic carriers have common properties with those in indolent ATLs. Clin Cancer Res; 20(11); 2851–61. ©2014 AACR.
We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 ؋ 10 7 /kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 ؋ 10 9 / L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 ؋ 10 9 /L was achieved in 16 patients at a median time of 49 days. Acute graft-versushost disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.
We report the results of unrelated cord blood transplantation (CBT) for 13 adult patients with advanced myelodysplastic syndrome (MDS). The median age was 40 years, the median weight was 51 kg, and the median number of infused nucleated cells was 2.43 ؋ 10 7 /kg. Twelve patients had myeloid reconstitution, and the median time to more than 0.5 ؋ 10 9 /L (5 ؋ 10 8 /L) absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 ؋ 10 9 /L was achieved in 11 patients at a median time of 49 days. Acute graft versus host disease (GVHD) occurred in 9 of 12 evaluable patients and chronic GVHD in 8 of 11 evaluable patients. Ten patients are alive and free of disease at between 171 and 1558 days after transplantation. The probability of disease-free survival at 2 years was 76.2%.
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