Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 andTRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3′-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia.

Summary. Cytomegalovirus (CMV) infection in 28 adult patients after cord blood transplantation (CBT) from unrelated donors was compared with that after bone marrow transplantation from HLA (human leucocyte antigen)-matched related (R-BMT) and unrelated (U-BMT) donors. Positive CMV antigenaemia was seen in 19 (79%) of 24 CMV-seropositive patients at a median of 42 d (range 29-85 d) after CBT, but in zero of four CMV-seronegative patients. This did not differ significantly from values observed after R-BMT and U-BMT (66%, P ¼ 0AE22, and 60%, P ¼ 0AE15 respectively). Based on the antigenaemia results, 16 patients (67%) received pre-emptive ganciclovir therapy from a median of 47 d (range 36-67 d) after CBT. This proportion was higher than that observed after R-BMT (28%, P ¼ 0AE0048), but did not differ from that after U-BMT (50%, P ¼ 0AE21). In addition, the probability of requiring more than two courses of ganciclovir therapy after CBT (21%) was higher than after R-BMT and U-BMT (0%, P ¼ 0AE015 and 0AE039 respectively). One patient (5%) developed CMV disease after U-BMT, whereas no patients developed CMV disease after CBT or R-BMT. The CMV serostatus, use of a steroid and HLA disparity affected the probability of requiring ganciclovir therapy after CBT (P ¼ 0AE024, 0AE032 and 0AE017 respectively). These results suggest that recovery of CMV-specific immunity after CBT is delayed when compared with BMT.

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.