The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Hematologic Neoplasms 383
The MLL gene at 11q23 is involved in a number of translocations with different partner chromosomes.
The more common translocations observed in childhood AML are t(9;11)(p21;q23) (see Fig. 1s)
and t(11;19)(q23;p13) (see Fig. 1pp). Other observed translocations of 11q23 involve approximately
20 different partner chromosomes (65).
Acute myeloid leukemia with associated abnormalities of 11q23 has an intermediate survival.
Acute Myeloid Leukemia with Multilineage Dysplasia
Acute myeloid leukemia with multilineage dysplasia characteristically shows more than 20% blasts
in blood or marrow with visible dysplasia in two or more myeloid cell lineages, generally including
megakaryocytes. By definition, dysplasia must be present in about 50% of the cells of at least two
lines (82), and these features must be present in pretreatment specimens. This entity could occur de
novo or follow MDS or myelodysplastic qualitative disorders, in which, according to WHO, cell
counts are close to normal but morphology is not.
Chromosome abnormalities in this subtype are similar to those found in myelodysplastic syndrome and
often involve gain or loss of major segments of certain chromosomes. Some of the common changes are
loss of chromosome 7 and 18, deletion of 17q, loss of chromosome 5 or deletion of 5q, gain of chromosomes
8, 9, 11, 19, and 21, deletion of chromosomes 11, 12p, and 20q, and less often specific translocations,
like t(2;11)(p21;q23) (see Fig. 1f), t(1;7)(p10;q10) (usually unbalanced; see Fig. 1b), and a
translocation involving chromosome regions 3q21 and 3q26. Abnormalities in the 3q26 region such as
inv(3)(q21q26) (see Fig. 2aaa), t(3;3)(q21;q26) (see Fig. 1h), or ins(3;3)(q21;q26) (see Fig. 1i) are associated
with multilineage AML and MDS with increased platelet production. inv(3)(q21q26) is also seen in
other types of AML and myeloid qualitative syndrome associated with thrombocytosis and increased bone
marrow megakaryocytes (83–86). t(3;21)(q21;q26) is usually therapy-related or associated with myeloid
leukemia as a secondary event at blasts crisis, whereas t(3;5)(q25;q34) (see Fig. 1j) is associated with
multilineage dysplasia without thrombocytosis. In this subtype of leukemia, multilineage dysplasia has an
adverse effect on the probability of achieving complete remission (84–86).
Acute Myeloid Leukemia and Myelodysplastic Syndrome, Therapy Related
Therapy-related or secondary AML and myelodysplastic syndrome (t-AML/t-MDS) arise as a
result of cytotoxic chemotherapy and/or radiation therapy. Two major types are recognized based on
the causative agent: those that are alkylating agent/radiation related and those that are topoisomerase
II inhibitor related (87–90). These types of AML and MDS can also be classified, if appropriate, by
the specific morphology originally seen with the qualifying term “therapy-related.”
The process of acute leukemia frequently presents initially as a myelodysplastic syndrome, with
evidence of bone marrow failure with isolated cytopenia or pancytopenia and associated myelodysplastic
changes. Frank dysplastic features in multiple cell lineages usually follow this stage, during
which the blast percentage in marrow is usually less than 5%.
Alkylating agent/radiation-related therapy-related AML, either presenting as AML or evolving
from MDS, usually involves all myeloid cell lines. High incidences of clonal cytogenetic abnormalities
are seen in this subgroup of leukemia. These abnormalities are similar to those seen in AML with
multilineage dysplasias, MDS, refractory cytopenia with multilineage dysplasia, or refractory anemia.
The common aberrations are unbalanced translocations or deletions involving chromosome 5
and/or 7, with the loss of all or part of the long arm of these chromosomes (see Fig. 2c,d,h,i,j,k). The
deletion of the long arm of chromosome 5 usually includes bands q22-q23 (87). Other chromosomes
frequently involved in a nonrandom manner include chromosomes 1, 4, 12, 14, and 18. Complex
nonspecific chromosomal abnormalities are the most common finding. Therapy-related leukemia
with multiple cytogenetic abnormalities is refractory to any leukemia therapy and is associated with
short or poor survival.
Topoisomerase II inhibitor-related AML characteristically has a significant monocytic component.
Most cases fall in the category of acute monoblastic or myelomonocytic leukemia. The predominant