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Chapter 41: Classification and Clinical Manifestations of the Clonal Myeloid Disorders

PATHOGENESIS

  • 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.

TABLE 41–1NEOPLASTIC (CLONAL) MYELOID DISORDERS
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TABLE 41–1 NEOPLASTIC (CLONAL) MYELOID DISORDERS

  1. Minimal-deviation neoplasms (no leukemic blast cells are evident in marrow)

    1. Underproduction of mature cells is prominent

      1. Clonal (refractory) sideroblastic anemiaa (see Chap. 42)

      2. Clonal (refractory) nonsideroblastic anemiaa (see Chap. 42)

      3. Clonal bi- or tricytopeniaa (see Chap. 42)

      4. Paroxysmal nocturnal hemoglobinuria (see Chap. 45)

    2. Overproduction of mature cells is prominent

      1. Polycythemia vera (see Chap. 43)

      2. Essential thrombocythemia (see Chap. 44)

  2. Moderate-deviation neoplasms (small proportions of leukemic blast cells usually present in marrow)

    1. Chronic myelogenous leukemia (see Chap. 47)

      1. Ph chromosome-positive, BCR rearrangement positive (~90%)

      2. Ph chromosome-negative, BCR rearrangement positive (~6%)

      3. Ph chromosome-negative, BCR rearrangement negative (~4%)

    2. Primary myelofibrosisb (chronic megakaryocytic leukemia) (see Chap. 48)

    3. Chronic eosinophilic leukemia (see Chaps. 34 and 47)

      1. PDGFR rearrangement positive

      2. FGFR1 rearrangement-positive

    4. Chronic neutrophilic leukemia (see Chap. 47)

    5. Chronic basophilic leukemia (see Chap. 47)

    6. Systemic mastocytosis (chronic mast cell leukemia) (see Chap. 35)

      1. KITD816V mutation-positive (~90%)

      2. KITV560G mutation-positive (rare)

  3. Moderately severe deviation neoplasms (moderate concentration of leukemic blast cells present in marrow)

    1. Oligoblastic myelogenous leukemia (refractory anemia with excess blasts)a (see Chap. 42)

    2. Chronic (syn. subacute) myelomonocytic leukemia (see Chap. 47)

      1. PDGFR rearrangement-positive (rare)

    3. Juvenile myelomonocytic leukemia (see Chap. 47)

  4. Severe deviation neoplasms (leukemic blast or early ...

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