Page 910 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 56 Conventional and Molecular Cytogenomic Basis of Hematologic Malignancies 793

using highly sensitive and specific PCR-based assays, is mandatory to be present initially, and evolutionary change may occur during the
determine the KIT allelic burden rapidly, which is now used as a gold course of the disease. Even at diagnosis, complex genomic lesions
standard for assessing disease burden. involving five or more different chromosomes are not unusual.
Despite heterogeneity of chromosomal defects (gain, loss, deletion,
amplification, rare balanced translocations, transcriptional silencing
MYELODYSPLASTIC SYNDROMES via methylation or point mutation), the unifying concept of genetic
instability in MDS is hemizygosity of specific genes or chromosomal
The MDSs (see Chapter 63) are a clinically heterogeneous group of regions. The most common chromosomal anomalies in MDS involve
hematologic neoplasms with differing biology and clinical manifesta- gain of 1q, del(5q)/−5, del(7q)/−7, trisomy 8, del(11)(q23), del(12p),
tions. They have in common a clonal origin, dysplastic cellular +13/del(13q), t(11q23), del(12p), del(17p), del(20)(q11q13), +21,
morphology, cytopenias, abnormalities of cellular maturation, and an and idic(X)(q13).
increased propensity to develop acute leukemia (20%–40%). They In 2012 a new cytogenetic classification of MDS was established
8
predominantly occur in elderly people as a result of multistep patho- that includes five different risk groups (Fig. 56.20 and Table 56.4).
genesis. Cytogenetic studies can provide both diagnostic and prog- The clinical relevance and the power of conventional cytogenetics
nostic information. A chromosomally abnormal clone can be detected in MDS were recognized by the WHO, which documented a strong
in 50% to 60% of patients with de novo MDS and in approximately association between del(5)(q13q33) and 5q− syndrome. The 5q−
90% of patients with therapy-related MDS. There appears to be a syndrome is a unique subtype of low-risk MDS with a favorable
correlation between the frequency of chromosomal abnormalities and prognosis, lack of other cytogenetic abnormalities, low rate of leuke-
the severity of disease. Approximately 35% of patients with less mic transformation, and more common occurrence in older adult
aggressive MDS, such as refractory anemia and refractory anemia females (see Fig. 56.20, second row).
with ring sideroblasts, have clonal chromosomal rearrangements, Among patients who do not have 5q− syndrome (with or without
whereas approximately 60% to 70% of patients with refractory other chromosomal abnormalities), interstitial deletions of the long
anemia with excess blasts in transformation have such chromosomal arms of chromosome 5 occur in 10% to 15% of patients and are
abnormalities. A single or complex chromosomal abnormality may among the most frequent chromosomal abnormalities in MDS (see

–y del(11)(q22q24)

Very good
prognosis
Y
X 11
del(5)(q22q25.1) del(20)(q11q13) Normal karyotype

Good
prognosis
20
5
del(7)(q21q32) +8 i(17)(q10) +19

Intermediate
prognosis
17 19
7 8
inv(3)(q22.2q26.2) t(3;3)(q21;q26) del(3)(q13q26) –7

Poor
prognosis

7
Monosomal karyotype
Very poor
prognosis

Fig. 56.20 PROGNOSTIC SIGNIFICANCE OF THE RECURRENT CHROMOSOMAL ABNOR-
MALITIES IN MYELODYSPLASTIC SYNDROME, ACCORDING TO THE NEW COMPREHENSIVE
CYTOGENETIC SCORING SYSTEM.