Incidence of involvement of the B and T lymphocyte lineages in chronic myelogenous leukemia

Abstract

Peripheral blood specimens were obtained from 22 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) (16 in chronic phase, 2 in an accelerated phase, and 4 in blast crisis). Studies were performed to determine the frequency of the presence of the Ph1 chromosome in cells of lymphoid lineages. Rosetted (E+) lymphocytes (T lymphocytes) from nine patients in chronic phase and one patient in blast crisis were stimulated with T cell growth factor interleukin 2 (IL-2) and/or phytohemagglutinin (PHA). All ten patients had sufficient T lymphocyte metaphases for analysis and of a total of 461 metaphases examined, only one contained the Ph1 chromosome. Nucleated cells of density less than 1.077 g/mL were infected with Epstein-Barr virus (EBV). Following infection, cell lines were established from individual colonies attached to egg albumin- coated Lab-Tek slide chambers (clonal cell lines) or from suspension culture in 96-well tissue culture cluster dishes (nonclonal cell lines). Cell surface and intracellular marker analysis confirmed the B lymphocyte phenotype of all the cell lines examined. B lymphoblastoid cell lines were established from 16 of the 22 patients. All lines from 12 patients were Ph1-negative. From two chronic phase patients, both Ph1-positive and Ph1-negative lines were established. From one patient in an accelerated phase, only Ph1-positive lines were established. From another patient in blast crisis (of myeloblastic phenotype), only Ph1- positive lines were established initially; however, five months later, after the patient had been treated with mitoxantrone, only Ph1-negative lines were derived from this patient. Based on these results, it appears that most B cells and mature T cells in most CML patients are Ph1-negative, but that about 25% of patients have predominantly Ph1- positive B cells or a mixture of Ph1-positive and Ph1-negative B cells that are capable of growing as established cell lines after transformation with EBV.

Low blood dendritic cells in chronic myeloid leukaemia patients correlates with loss of CD34+/CD38– primitive haematopoietic progenitors

“…Alternatively, and in view of our in vitro results, the causes of DC reduction may be central, with a decreased production of DC from primitive haematopoietic stem cells. Different lines of evidence placed the malignant transformation in CML closer to, if not in, the pluripotential stem cell (Nitta et al , 1985). Therefore, ‘dendritopoiesis’ in CML is likely to be affected by the leukaemic process that induces a marked expansion of granulopoietic progenitors to the detriment of other populations.…”

CD7 expression by CD34+ cells in CML patients, of prognostic significance?

“…Chronic myelogenous leukemia is a myeloproliferative disease, and whether the lymphoid lineages are part of the clonal disorder has been a matter of controversy (29–31). As expected, a relative number of CD34 + CD33 + cells increased in CML.…”

Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies

“…19,[100][101][102][103] The presence of the Ph chromosome in erythrocyte, granulocyte, monocyte, and megakaryocyte precursors indicates that the original transformation occurred in an ancestral stem cell common to these cell types; it is absent in the majority of mature lymphocytes, although in about 20-25% of patients in chronic phase some of the B cells contain the Ph marker and early B-cell progenitors predominate in about 25% of patients in blastic transformation. 73,74,78,104 However, the level of expression of p210 bcr-abl in Epstein-Barr virus transformed B-cell lines that retain Bcr-Abl is lower and more variable than in myeloid cell lines derived from patients in blastic phase 105 T-lymphocytes have only rarely been found to be Ph+ either during the chronic or blastic phases of the disease, 106,107 but bilineal (T lymphoid/myeloid) Ph+ progenitors may be involved in some cases of blastic transformation, 108 and quadralineal involvement was reported in one patient with Ph+ ALL. 109 It was recently reported that variable proportions of endothelial cells in CML patients contain the Bcr-Abl fusion gene, suggesting that they may be derived from a common hemangioblastic progenitor cell 110 .…”