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1384 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1385

TABLE 88–4. Clinical Correlates of Frequent Cytogenetic Abnormalities Observed in Acute Myelogenous Leukemia
Chromosome
Abnormality Genes Affected Clinical Correlation
Loss or gain of chromosome
Deletions of part or all Not defined Frequent in patients with acute myelogenous leukemia (AML) occurring de novo and in
of chromosome 5 or 7 patients with history of chemical, drug, or radiation exposure and/or previous hematologic
disease. 282,283,286,287
Trisomy 8 Not defined Very common abnormality in acute myeloblastic leukemia. Poor prognosis, often a secondary
change. 283,289
Translocation
t(8;21) (q22;q22) RUNX1(AML1)– Present in ~8% of patients <50 years old and in 3% of patients >50 years old with AML.
288
RUNX1T1(ETO) Approximately 75% of cases have additional cytogenetic abnormalities, including loss of Y in
males or X in females. Secondary cooperative mutations of KRAS, NRAS, KIT common. Present
in ~40% of myelomonocytic phenotype. Higher frequency of myeloid sarcomas. 263–266
t(15;17) (q31; q22) PML-RAR-α Represents ~6% of cases of AML. Translocation involving chromosome 17, t(15;17), t(11;17),
288
or t(5;17) is present in most cases of promyelocytic leukemia. 290,291
t(9;11); (p22; q23) MLL (especially Present in ~7% of cases of AML. Associated with monocytic leukemia. 292,293 11q23 transloca-
MLLT3) tions in 60% of infants with AML and carries poor prognosis. Rearranges MLL gene. 292–296 Many
translocation partners for 11q23 translocation. 295–298 MLL1, MLL4, MLL10 may also result in
AML phenotype.
t(9;22) (q34; q22) BCR-ABL1 Present in ~2% of patients with AML. 299,300
t(1;22)(p13;q13) RBMIS-MKL1 <1% of cases of AML. Admixture of myeloblasts, megakaryoblasts, micromegakaryocytes
with cytoplasmic blebbing, dysmorphic megakaryocytes. Reticulin fibrosis common. 301
t(10;11) PICALM-MLLT10 Outcome similar to that of intermediate prognosis group; more extramedullary disease and
(p12-13;q14-21) CD7 expression. 302
Inversion
Inv(16) (p13.1;q22) or CBF-β MYH11 Present in ~8% of patients <50 years of age and in ~3% of patients >50 years of age with
t(16;16) (p13.1;q22) AML ; often acute myelomonocytic phenotype; associated with increased marrow eosino-
288
phils; predisposition to cervical lymphadenopathy, better response to therapy. 304–307 Predis-
303
posed to myeloid sarcoma.
Inv(3) (q21q26.2) RPN1-EVI1 ~1% of cases of AML. Approximately 85% of cases with normal or increased platelet count.
Marrow has increased dysmorphic, hypolobulated megakaryocytes. Hepatosplenomegaly
more frequent than usual in AML. 308

SPECIAL CLINICAL FEATURES upregulation of endothelial cell intercellular adhesion molecule-1 and
Hyperleukocytosis of leukemic blast cell lymphocyte function-associated antigen-1 may
mediate the vessel wall interaction contributing to leukostasis.
349
Leukocyte count is an independent prognostic factor in the out-
come of AML treatment. Approximately 5 percent of patients with Hypoplastic Leukemia
330
AML develop signs or symptoms attributable to a markedly elevated Approximately 10 percent of patients with AML present with a syn-
blood blast cell count, usually greater than 100 × 10 /L (Chap. 83). drome that includes pancytopenia, often with inapparent blood blast
331
9
Several subsets of AML are associated with a greater likelihood of cells, and absence of hepatic, splenic, or lymph nodal enlargement. 350–352
presenting with hyperleukocytosis. These include acute myelomono- If one corrects for the decrease in marrow cellularity with age, hypoplas-
cytic, acute monocytic, the microgranular variant of APL, and AML tic AML occurs in approximately 2 percent of cases. Approximately
353
with inv16,11q23 rearrangements, or FLT3-ITD. The circulations of the 75 percent of these patients are men older than 50 years of age. Marrow
CNS, lungs, and penis are most sensitive to the effects of leukostasis. biopsy is hypocellular, which is the unusual feature of the syndrome,
Intracerebral hemorrhage from vascular occlusion, invasion, and dis- but leukemic blast cells are evident and present in a proportion of
ruption, sometimes complicated by thrombocytopenia and vascular 10 to 90 percent of marrow cells. Response to intensive chemotherapeu-
insufficiency are the most virulent manifestations of the syndrome. 332–336 tic treatment, often with low-dose cytarabine because of the patients’
Dizziness, stupor, dyspnea, and priapism may occur. Diabetes insip- very advanced age, has been relatively good, and 3-year survival rates
idus is another association. 337,338 Other severe organ involvement also are approximately the same as the rates of other age-matched patients. 354
may occur infrequently. A high early mortality in patients with AML
correlates with hyperleukocytosis greater than 100 × 10 /L. 334,335,339,340 Oligoblastic Myelogenous (Subacute, Smoldering, Low-
9
Chemotherapy in hyperleukocytic patients may lead to a pulmonary Infiltrate, Pauciblastic) Leukemia
leukostatic syndrome, presumably from the effects of rigid, effete blast Not infrequently, usually in patients older than 50 years of age, myel-
cells, or the discharge of large amounts of cell contents and resultant ogenous leukemia is manifested by anemia and often thrombocytope-
cell aggregation or other effects. 341–343 Larger-vessel vascular occlusion nia. The leukocyte count may be low, normal, or increased, and a small
as a result of white thrombi or masses of leukemic cells is rare. 344,348 The proportion of blast cells are present in the blood (0 to 15 percent) and

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