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  • Result from a mutation(s) of DNA within a single pluripotential marrow hematopoietic cell or very early progenitor cell. Mutations disturb the function of the gene product.

  • Overt cytogenetic abnormalities can be found in 80 percent of cases of acute myelogenous leukemia (AML) in experienced laboratories (see Williams Hematology, 8th ed, Chap. 11, Fig. 11–3, p. 153).

    — Translocations (e.g., t(15;17)) and inversions of chromosomes (e.g., inv16) can result in the expression of fusion genes that encode fusion proteins that are oncogenic.

    — Overexpression or underexpression of genes that encode molecules critical to the control of cell growth or programmed cell death, often within signal transduction pathways or involving transcription factors occur.

    — Deletions of all or part of a chromosome (e.g., 5q- or -7) or duplication of all or part of a chromosome may be evident (e.g., trisomy 8).

  • An early multipotential hematopoietic cell undergoes clonal expansion but retains the ability to differentiate and mature, albeit with varying degrees of pathologic features, into various blood cell lineages.

  • The result is often abnormal blood cell concentrations (either above or below normal), abnormal blood cell structure and function; the abnormalities may range from minimal to severe.

  • Resulting disease phenotypes are numerous and varied because of the nine differentiation lineages from a multipotential hematopoietic cell.

  • Neoplasms that result can be grouped, somewhat arbitrarily, by the degree of loss of differentiation and maturation potential and by the rate of disease progression.

  • Most patients can be grouped into the classic diagnostic designations listed in Table 41–1.


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