Changes in self‐renewal potential of human leukemic cells (K562): A bidirectional stochastic process

Abstract

Daughter cells arising from a single cell division in the leukemic cell line K562 have equivalent self-renewal potential with respect to their ability to form clones in semisolid medium. However, individual cells isolated from these clones in sequence have vastly different abilities in their self-renewal potentials. Thus, cells originating from a clone with any particular self-renewal potential exhibit the full range of self-renewal potentials--from highly renewing to none renewing, cells. These results show that self-renewal potential in the K562 cell line is a random, reversible and partially noninherited characteristic. It is suggested that the stochastic variability of the intraclonal self-renewal potential of K562 progeny cells either reflects the initial expression of a differentiation program or the expression of the predeterministic portion of the normal myelopoietic differentiation pathway.

Commitment to differentiation of human promyelocytic leukemia cells (HL60): An all‐or‐none event preceded by reversible losses of self‐renewal potential

“…An easily measurable parameter was required to quantify phenotypic changes occurring in individual clones between consecutive divisions. Such parameter was provided by the observed symmetry of self-renewal of HL60 sister cells, which is similar to that previously reported for K562 cells, a human chronic myeloid leukemia in blastic transformation (von Melchner and Hoffken, 1985).…”

“…This random process can be approximated by a cumulative gammadistribution (Fig. 4) and is essentially similar to that described for normal (Till et al, 1964) and transformed (von Melchner and Hoffken, 1985) multipotential stem cells.…”

“…A decrease of self-renewal potential between consecutive cell divisions is reflected by a clonogenic potential index below 1, whereas an index value above 1 reflects an increase of self-renewal potential. A change of the clonogenic potential index from less than 1 to greater than 1 reflects a "reversal" of self-renewal potential (von Melchner and Hoffken, 1985). It can be seen in Figure 3A, that the self-renewal potential of consecutive progeny cells increases and decreases randomly.…”

“…Using a previously described experimental system of sequential daughter cell transfers in semisolid medium (von Melchner and Hoffken, 1985) we have analysed selfrenewal and differentiation in single clones exposed to all-trans retinoic acid or DMSO.…”