Studies on Human Preleukaemia II In Vitro Colony Forming Capacity in Aregenerative Anaemia with Hypercellular Bone Marrow

Abstract

The colony and cluster forming capacity of bone marrow and mononuclear leucocytes and colony:cluster ratio (CCIR) was studied in 23 patients with resistant anaemia and hypercellular bone marrow. Bone marrow controls included 28 patients with iron deficiency, haemolytic, megaloblastic and secondary anaemia as well as 15 haematologically normal subjects and 13 healthy volunteers. Colony formation by blood leucocytes was studied in aregenerative anaemias and in 13 healthy volun‐Colonies and clusters were grown in soft agar cultures in vitro from all control subjects. In normal volunteers the marrow grew between 24 and 201 colonies and 37 to 212 clusters/105 cells with the CCIR of 0.48–2.50. Blood leucocytes produced 6–184 colonies and 6–88 clusters/106 mononuclear cells with CCIR 0.43–2.64. Colony formation and CCIR were largely normal in haematologically intact subjects and patients with anaemia of known etiology. Patients with aregenerative anaemia showed abnormal colony formation by bone marrow and blood cells more often (P < 0.01) than control groups. Only 7 of 23 patients had colony formation within the normal range. Blood leucocytes in 12 out of 18 aregenerative anaemias failed to grow colonies in vitro. The marrow CCIR was below the normal range in all aregenerative anaemias with defective and in 3 with normal colony formation and was significantly lower than in the controls (P < 0.01). Of 19 aregenerative anaemias with defect colony formation 11 died, 7 with acute leukaemia. The in vitro colony formation appears useful for subclassification of anaemic conditions and for identification of patients who may be at higher risk of developing leukaemia.

Erythroid and granulocyte‐macrophage colony formation in myelodysplastic syndromes

“…Granulocyte-macrophage colony formation in myelodysplastic syndromes has been in-vestigated in a number of studies (1)(2)(3)(4)(5)(6)(7)(8). The present results are in general similar to those obtained in previous studies, although the % of patients with normal CFU-GM colony formation was higher in this study than in most others.…”

“…Myelodysplastic syndromes (preleukaemia) are a heterogenous and variably-defined group of disorders. The in vitro formation of colonies by granulocyte-macrophage progenitors from the marrow of patients with these diseases has been investigated in several studies, and abnormal growth patterns have been found in a varied proportion of patients (1)(2)(3)(4)(5)(6)(7)(8). The abnormalities are similar to those seen in acute myeloid leukaemia: reduced formation of colonies or excessive growth of colonies and/or smaller aggregates, clusters.…”

Production of tumor necrosis factor and granulocyte colony stimulating factor by bone marrow accessory cells in myelodysplastic patients

“….7 pg/ml, RARS 11 k 5.8 pg/ml, CMML 12.5 f 3.7 pg/ml, RAEB 4.712.7 pg/ml, RAEB-t 4 . 0 1 2.3 pg/ml).In keeping with previous data reported in the literature(16)(17)(18)(19), growth of bone marrow HPC was significantly reduced (p <0.01) in MDS patients versus controls (CFU-GM: 26.1 1 8.1 colonies/2 x…”

Progression of Bone Marrow Abnormalities in Malignant Hemopoietic Dysplasia

“…When more adequate therapeutic measures become available, it should be of great value to identify patients who are liable to develop malignancy. The in vitro culture technique of cloning stem cells from the bone marrow is useful for identifying malignant patients, but does not differentiate preleukemic patients from those who die from cytopenic complications (2,16). A careful cytological evaluation in sequential bone marrow samples, using a simple scoring system a s outlined in the present study, can be a complementary method for identifying patients in the malignant group who are liable t o develop overt leukemia within a short time.…”