Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells

Abstract

The treatment of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder has improved recently, but most patients have not yet been cured. Some patients develop resistance to the available tyrosine kinase treatments. Persistence of residual quiescent CML stem cells (LSC) that later resume proliferation is another common cause of recurrence or relapse of CML. Eradication of quiescent LSCs is a promising approach to prevent recurrence of CML. Here we report on new biophysical differences between quiescent and proliferating CD34+ LSCs, and speculate how this information could be of use to eradicate quiescent LSCs. Using AFM measurements on cells collected from four untreated CML patients, substantial differences are observed between quiescent and proliferating cells in the elastic modulus, pericellular brush length and its grafting density at the single cell level. The higher pericellular brush densities of quiescent LSCs are common for all samples. The significance of these observations is discussed.

Atomic Force Microscopy Detects the Difference in Cancer Cells of Different Neoplastic Aggressiveness via Machine Learning

“…[ 3-5 ] All this wealth of information can be used to address important medical questions, for example, the problems of cancer detection. There is a host of works reporting the differences in the mechanical properties of cancer and normal cells, [ 6,7 ] cancer cells of different metastatic activity, [ 4,5,8 ] and even cancer‐initiating cells. [ 9 ] It was also found that cancer cells of different aggressiveness have a substantially different pericellular coat, a layer of molecules grafted to the pericellular membrane surrounding cells.…”

“…[ 1,2 ] Further development of AFM modes has shown that the AFM technique can also be used to obtain information about the pericellular layer, a layer of molecules grafted to the pericellular membrane surrounding cells. [ 3-5 ] All this wealth of information can be used to address important medical questions, for example, the problems of cancer detection. There is a host of works reporting the differences in the mechanical properties of cancer and normal cells, [ 6,7 ] cancer cells of different metastatic activity, [ 4,5,8 ] and even cancer‐initiating cells.…”

“…[ 9 ] It was also found that cancer cells of different aggressiveness have a substantially different pericellular coat, a layer of molecules grafted to the pericellular membrane surrounding cells. [ 3-5 ] The challenge of using these properties to identify the cell phenotype lies in the difficulty of controlling cell physical properties during sample preparation. It was shown, for example, that the elastic modulus and pericellular coat of cells can change during sample preparation substantially more than the difference between cancer and normal cells.…”

Mechanical properties of cancer cells depend on number of passages: Atomic force microscopy indentation study

“…[10][11][12] The study of this physical side of the disease at the single cell level gives a novel fundamental insight of the diseases. 13,14) Furthermore, it helps to develop new method of diagnosis of those diseases. 2) The majority of reports of the study of cell mechanics deal with not primary cells extracted from individual tissues but rather with cell lines, primarily distributed by the American Type Culture Collection (ATCC).…”

AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell–cell communication

“…Therefore, the study of biomechanical properties of cells is of fundamental interest. Furthermore, biomechanical properties of single cells in vitro or ex vivo and its pericellular interface have recently attracted a lot of attention as a potential physical biomarker of various diseases, and even might be used for prognostics [1][2][3][4].…”