The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Hematologic Neoplasms 379
The del(5q) Syndrome
A major category in this subgroup is the group of patients with isolated 5q deletion syndrome
[del(5q), formerly referred to as 5q–]. This syndrome primarily occurs in women and is characterized
by megakaryocytes with hypolobated nuclei and refractory microcytic anemia, normal or
increased platelet count, and a favorable clinical course. Symptoms are usually related to refractory
anemia, which is often severe. The platelet count is generally normal to elevated and occasional
blasts, usually less than 5%, are seen. Erythroid precursor cells show dysplastic features of
varying degrees. Cytogenetically, this is a very special subgroup, as the sole cytogenetic abnormality
involves a deletion of chromosome 5 with breakpoints in the long arm from q31 to q33 (see Fig. 2c,d).
The size of the deletion and exact breakpoints are variable from case to case, and most deletions
are interstitial. In the WHO classification, this syndrome has been recognized as a specific subtype
of MDS because of the significance of isolated deletion 5q and relatively good prognosis. The
significance of more than 5% marrow blasts in patients with an associated deletion of chromosome
5 is not clear. Some reports indicate that these patients have a worse prognosis than those with
fewer than 5% blasts (64).
Karyotypic evolution is uncommon. In more complex cases, in addition to the del(5q), other
cytogenetic abnormalities including deletion of 17p with TP53 mutation and more complex chromosomal
changes are seen. When present, these are generally associated with an unfavorable clinical
course. Other cytogenetic abnormalities, such as deletion of 2q, are associated with involvement
of erythroid cells and megakaryocytes. Abnormalities of chromosome 3 are associated with MDS
and AML with increased megakaryocytes. Additional cytogenetic abnormalities are associated with
evolution to AML or a higher-grade myelodysplastic process. However, if any additional chromosome
abnormalities are present, the case should not be placed in the category of isolated 5q deletion
syndrome.
ACUTE MYELOID LEUKEMIA
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The leukemia cells
or blasts represent progenitors that are arrested in differentiation at a very early stage of myelopoiesis.
AML is characterized by an accumulation of granulocyte or monocyte precursors in the bone
marrow and blood. There is an increasing recognition of the importance of genetic events in the
classification and therapy of AML, making it an excellent model for studying genetic regulation of
differentiation and cancer progression.
Worldwide, the overall incidence of acute leukemia is approximately 4 per 100,000 per year, with
70% of these cases being acute myeloid leukemia. The vast majority of cases of AML occur in adults,
and the median age is about 60 years with an incidence of 10 per 100,000 population per year in
individuals 60 years and older. The possible etiological factors associated with leukemia and
myelodysplastic syndrome include viruses, ionizing radiation, cytotoxic chemotherapy, and benzene.
Cytogenetically, AML is a very heterogeneous disease, with more then 160 recurrent structural
chromosomal abnormalities having been reported (65,66). Molecular dissection of many reciprocal
translocations and inversions has resulted in cloning of the chimeric genes involved in tumorigenesis.
The significance of cytogenetic studies of AML is twofold. First, it has significantly increased our
knowledge of basic genetic mechanisms involved in tumorigenesis, thus contributing to our understanding
of the remarkable histopathological, immunophenotypic, and clinical heterogeneity of AML.
In the process of characterizing these specific chromosomal changes, which include translocations,
inversions, deletions, and duplications, scientists have cloned many known genes involved in leukemogenesis.
Second, chromosomal aberrations, irrespective of whether they are cloned molecularly,
help as tumor markers for diagnostic and prognostic purposes. The incidence of karyotypes with
clonal chromosomal aberrations in children with gene rearrangements is reported to be between 68%
and 85% and has generally been higher than that in adults.