Chromosomes and Tumor Progression.
Chromosome studies suggest that most neoplasms are unicellular in origin (i.e., "clones"), and that biological progression, typically associated with loss of "differentiated" properties, results from acquired genetic instability in the neoplastic population leading to sequential appearance of increasingly mutant subpopulations with greater selective growth advantage. In these circumstances acquisition by the tumor of an apparent "defect in maturation" could reflect either abnormal response to external growth regulators or loss ability to synthesize certain special differentiation products. Karyotypic data from a variety of mammalian neoplasms support both possibilities. The terminal accelerated phase of chronic granulocytic leukemia, for instance, in which undifferentiated blast cells replace a previously well-differentiated population, seems to represent emergence of a subline, often recognizable cytogenetically, in which an additionally altered response to growth regulation further shifts the balance between proliferation and differentiation at the stem cell level, so that undifferentiated (proliferating) cells come to predominate. In a case of chronic T cell leukemia, on the other hand, we have observed loss of certain specific T cell characteristics (membrane markers, response to mitogens) in conjunction with emergence of a chromosomally abnormal subclone, without alteration in the "mature" morphology of the neoplastic lymphocytes or any apparent change in their proliferation kinetics in vivo. Presumably, loss of these differentiated characteristics reflects alterations in specific gene functions within the neoplastic subpopulation, rather than any significant expansion in the undifferentiated stem cell pool. Cytogenetic studies may provide clues to the genetic basis of both types of "dedifferentiation.
D002869:Chromosome Aberrations / Q000473:pathology; D025063:Chromosome Disorders; D002875:Chromosomes / Q000648:ultrastructure*; D002999:Clone Cells / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000648:ultrastructure; D007951:Leukemia, Myeloid / Q000648:ultrastructure; D008297:Male; D009369:Neoplasms / Q000648:ultrastructure*; D013997:Time Factors