Malignant B-cells have receptors for and respond to interleukin-2

Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL-2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors.     

Effects of retinoids on in vitro differentiation of bone marrow cells in the myelodysplastic syndrome

The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.     

Response to Treatment in Acute Non-lymphatic Leukaemia: Prognostic Value of Colony Forming and Colony Stimulating Capacities of Bone Marrow and Blood Cells Compared to Other Parameters

Growth of bone marrow and mononuclear white blood cells (MWBC) in soft-agar cultures was studied in 26 patients with untreated acute non-lymphocytic leukaemia (ANLL). Marrow and MWBC from 30 healthy volunteers served as controls. All ANLL patients revealed an abnormal growth in vitro . Patients with an increased number of clones in marrow cultures and large cluster predominance ('excessive growth') responded poorly to therapy with only one of 10 patients entering remission. On the contrary, only two of the 15 patients with a decreased clone number ('low growth') failed to achieve remission. The number of colonies and clusters in both bone marrow and blood cultures was significantly lower at presentation in patients who later entered remission than in those who did not. The correlations between the number of colonies and clusters in the blood and the marrow cultures were statistically significant. No significant correlations were found between prognosis or colony formation, on one hand, and the production of colony stimulating activity (CSA), by bone marrow and blood cells of ANLL patients, on the other. Nor could such correlations be found between prognosis, blood cell counts, and age. It is concluded that the growth pattern of both bone marrow and circulating colony forming cells is of value in predicting the response to cytostatic drugs and particularly in selecting patients with a high probability to respond poorly to current cytostatic regimes.     

Accumulation of vincristine and doxorubicin in malignant lymphocytes with different immunophenotypes

Cellular accumulation of vincristine (VCR) and doxorubicin (DOX) was studied in 15 patients with low-grade B-cell malignancies. Their leukemic lymphocytes were isolated and the effect of verapamil on drug uptake was studied. The immunophenotype was characterized using anti-IgM, -IgD, -B 1, monoclonal antibodies. The more that cells bound the IgD or B1 antibodies, the more vincristine and doxorubicin did they accumulate. The fewer the cells that bound IgM antibodies, the more drug did they accumulate.     

Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: Differences in cellular DNA content

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS-AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feul-gen-stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS-AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; Dl) in each cell population was determined using a digital video-based imageanalyzing system (CAS-100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS-AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit Dl was found both in immature and mature bone marrow cells. Patients with MDS-AML had those of Dl values similar to normal controls. In consequence, a significantly reduced mean Dl was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS-AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA-DR expression, these data suggest biological differences between the two diseases. © 1993 Wiley-Liss, Inc.     

Effect of phytohemagglutinin and interleukin-2 on malignant and nonmalignant B and T lymphocytes

Peripheral blood mononuclear cells (PBMC) from patients with acute myeloid leukemia (AML) or non-Hodgkin lymphoma (NHL) and healthy controls were stimulated with phytohemagglutinin (PHA) and interleukin-2 (IL-2). PHA (1 microgram/ml) induced higher 3H-thymidine incorporation than 800 U/ml IL-2 in PBMC from both controls and patients with AML in complete remission. A synergistic effect between PHA and IL-2 was found. Malignant B cells from 5/12 NHL expressed IL-2 receptors and showed proliferative response to IL-2, but not to PHA. PHA induced higher cytotoxicity toward AML blasts in lymphocytes from healthy controls than did IL-2. In addition, PHA induced higher cytotoxicity in lymphocytes from healthy controls than in those from patients with AML in remission. In contrast, no difference in cytotoxicity between controls' and patients' lymphocytes was found after stimulation with IL-2. No HLA restriction could be demonstrated. Normal peripheral blood mononuclear cells and leukemic blasts from 2/12 AML were completely resistant to cytotoxic cells even at effector:target ratios four times as high as those otherwise required.