In vitro culture studies of blood and marrow cells in chronic myeloid leukemia at different phases of the disease

Abstract

The in vitro culture growth of peripheral blood (PB) and bone marrow (BM) cells were studied simultaneously from 100 adult patients with chronic myeloid leukemia at different phases. Sixty-five patients were investigated at initial diagnosis, 30 patients in control phase, and 41 patients in blast phase. In untreated chronic phase, the relative concentrations of granulocyte-macrophage progenitor cells (CFU-GM) in BM were not significantly different from those of normal controls, but there was generally a marked increase in circulating CFU-GM. The 6 Ph1-negative patients did not show different growth characteristics. We were unable to correlate the CFU-GM number to any of the hematologic parameters as well as to the response to busulfan therapy. Pretreated patients with excessive cluster formation did not necessarily indicate impending blast crisis. In hematologic remission, the numbers of CFU-GM in both BM and PB were well within the ranges of normal controls. Culture results in blast phase revealed a spectrum of abnormal growth. In myeloid crisis, 14/29 BM and 12/29 PB samples showed increased colony and cluster formations which were composed predominantly of immature cells with variable degeneration. Marrow cells in lymphoid crisis produced low numbers of both colonies and clusters in 5 out of 8 patients, while blood cells from 8 out of 10 patients formed large amount of colonies of normal morphology. This study indicates that the in vitro CFU-GM assay may have diagnostic utility in differentiating lymphoid crisis from myeloid crisis.

Growth advantage of chronic myeloid leukemia CFU-GM in vitro : survival to growth factor deprivation, possibly related to autocrine stimulation, is a more common feature than hypersensitivity to GM-CSF/IL3 and is efficiently counteracted by retinoids ± α-interferon

“…However, to further minimise the chance of collecting residual normal progenitors, PB cells were used in most experiments. Indeed, CFU-GM frequency is quite higher in CML than in normal PB; 38 moreover, PB was demonstrated to be more apt than BM in maintaining long-term growth of CML progenitors. 39 In order to minimise paracrine CSF production by accessory cells, in most experiments CFU-GM were enriched by removal of erythroid, lymphoid and mature myeloid cells.…”

Is there really an accelerated phase of chronic myeloid leukaemia?

“…In persons with chronic phase CML blood granulocyte concentration increases appropriately in infections and in rare persons with cyclical neutropenia and chronic phase CML the blood granulocyte concentration cycles like persons with cyclical neutropenia without CML. Lastly, in untreated chronic phase CML the blood granulocyte concentration usually reaches an stable apogee [8][9][10]. Moreover, the gene expression profile (GEP) of chronic phase CML cells resembles normal CD34-postive cells [11].…”

Production of Colony-Stimulating Activity by Circulating Leukocytes from Patients with Chronic Myeloid Leukemia at Various Phases of the Disease

“…Furthermore, pre vious studies on a very small number of patients gave conflicting results [4][5][6]. In an attempt to clarify these contradictory results, the present study, which included a very large patient population, was de signed (1) to determine the production of CSA by pe ripheral blood leukocytes (PBL) from patients with CML at different phases; (2) to relate the PBL CSA to the number of CFU-GM in their BM and PB; (3) to evaluate the relationship between the PBL CSA and the WBC counts and/or differentials in the PB as well as in the feeder layers. …”

“…We have shown that bone marrow (BM) and peripheral blood (PB) cells from patients with chronic myeloid leukemia (CML) at various stages of the disease ex hibited different growth characteristics [3]; there was a marked increase in circulating CFU-GM number in the untreated chronic phase of CML; hematologi cal remission was usually associated with a return toward normal in the number of CFU-GM, and cul ture results in blast phase revealed a spectrum of ab normal growth patterns which had diagnostic utility in differentiating lymphoid crisis from myeloid cri sis. The in vitro culture systems provide techniques not only for examining the myeloid progenitor cells but also for assessing the cellular and humoral fac tors involved in hemopoiesis.…”