No abstract

Human peripheral blood contains two populations of dendritic cells (DC) but their developmental relationship has not been established. Freshly isolated CD11c– DC possessed a lymphoid morphology, lacked myeloid markers but expressed lymphoid markers (CD4+ CD10+) whilst the CD11c+ DC were monocytoid in appearance and expressed myeloid markers. Although both populations were allostimulatory, only the CD11c+ DC were able to take up antigen. Irrespective of the culture conditions the CD11c– cells developed into CD11c– CD13– CD33– CD4+ CD1a– CD83+/– DC. In contrast, cultured CD11c+ cells developed the phenotype CD11c+ CD13+ CD33+/– CD4– CD1a+ CD83+ CD9+. Only the CD11c+ DC expressed macrophage colony‐stimulating factor (M‐CSF) receptor and gave rise to CD14+, esterase+, phagocytic macrophages when cultured in M‐CSF. These data suggest that these two populations of DC represent distinct lineages of antigen‐presenting DC.

investigated for BCR-ABL transcripts with 2 different polymerase chain reaction (PCR) methods as previously described in detail. 1,2 Forty-six (1.8%) cases showed an ambiguous result and were not considered for further analysis. Of the remaining 2498 cases, 904 (36.2%) were BCR-ABL ϩ (599 ϭ 24% minor breakpoint region [m-bcr] and 282 ϭ 11.3% major breakpoint region [M-bcr], 15 ϭ 0.6% both, M-bcr and m-bcr, and 8 atypical transcripts), and 1594 were BCR-ABL Ϫ . Atypical transcripts were not systematically detected before 2000 1 and thus had to be excluded from further analysis. We grouped patients into age cohorts at 10-year intervals according to their age at diagnosis, each comprising between 277 and 481 patients and found a remarkable increase of BCR-ABL frequency in adolescents and young adults ( Figure 1). It increased from 12.7% in adolescents (15-24 years) to 30.6% and 43.7% in patients aged 25 to 34 and 35 to 44 years, respectively. In patients older than 44 years, the BCR-ABL frequency showed no further increment and ranged between 42% and 44%. The increase of BCR-ABL frequency was paralleled by a relative increase of M-bcr transcripts. These transcripts accounted for 16.4% of all BCR-ABL-positive cases in adolescents (15-24 years). Their relative frequency increased to 22.5% in 25-to 34-year-olds and to 36.8% in 35-to 44-year-olds and remained between 33% and 36.2% from then on.The reason for this age dependency is not obvious. The relative frequencies of immunologic subtypes (78.2% common, 19.9% pre-B, 1.9% pro-B) of BCR-ABL ϩ patients did not differ significantly across the age groups. Moreover, the frequency of BCR-ABL was also not significantly different in woman compared with men. Our study excluded lymphatic blast crises in patients with known chronic myeloid leukemia (CML). Previous work has indicated that M-bcr-and m-bcrpositive ALL may arise from different sets of hematopoietic progenitor cells, 3 but this does not explain the age dependency. A number of genetic markers in ALL show a marked age dependency (reviewed in Armstrong and Look 4 ), eg, TEL-AML1, TLX1, and TLX3, MLL aberrations (especially in infant ALL). Our data provide additional information on the biology of BCR-ABL-positive ALL and substantiate evidence of age-dependent variation in the genetic background of ALL.

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72 percent, and the actuarial risk of relapse was 7 percent. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18 percent, and the actuarial risk of relapse was 42 percent. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established.

A simple assay was developed to assess the potential of patients with acute myelogenous leukaemia (AML) to respond to immunotherapy. Lymphocytes, monocytes and leukaemic blasts with their corresponding intracellular cytokine profiles were evaluated by four-colour flow cytometry. In 50 ll samples of whole blood, surface labelling for CD45, CD8 and CD3 was used for cell identification prior to intracellular staining for interleukin (IL)-4, IL-10, IL-12 and interferon (IFN)-c. Absolute numbers of CD8 + and CD8 À (putative CD4 + ) T-cells, NK cells (CD8 + /CD3 À ) and monocytes were determined by reference to a fixed number of added fluorescent beads. The absolute numbers of CD8 À and CD8 + T-cells in the blood of patients with AML were similar to those of normal controls. More of the lymphocytes in the blood of leukaemic patients spontaneously produced cytokines compared with those of controls. Furthermore, primary AML blasts secreted predominantly IFN-c. After recovery from chemotherapy, lymphocyte counts tended to be lower than in normals and reduction of NK cells reached significance after the second chemotherapy (P ¼ 0.01). A prominent CD8 lo /CD3 lo-int lymphocyte subset appeared after recovery in some patients. This laboratory application of the study of cell subsets and intracellular cytokines in patients undergoing treatment may be helpful in monitoring immunological responses in AML.