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Paridar et al. BCR-ABL and myelodysplastic syndrome

morphological BM examination. According to the 2016 Giemsa (MGG) staining, myeloperoxidase staining,
WHO revision, MDS patients are divided into lower- nonspecific esterases (especially for CMML), as well
and higher-risk MDS. Lower-risk MDS conditions that as iron staining and assessment of cytopenia. MDS
[12]
have below 5% of blasts include: MDS with single- diagnosis is often challenging for several reasons, such
lineage dysplasia, MDS with single-lineage dysplasia as varying clinical manifestations in different patients
and ring sideroblasts (RS), MDS with multilineage and the absence of dysplasia in some cases. For this
dysplasia without RS and with RS, MDS with isolated reason, cytogenetic tests have been introduced for
del (5q), and MDS unclassifiable (MDS-U). Higher-risk correct diagnosis of some MDS subtypes; for example,
MDS conditions (5-19 blasts) include: MDS-EB1 (5- in the fourth classification of WHO, del 5q is considered
9% blast and/or 2-4% in PBS) and MDS-EB2 (10-19% as a separate subgroup. In patients whose diagnosis
blasts; Auer rods, or 5-19% in PBS). [5] is controversial, cytogenetic analysis seems to be a
helpful addition to clinical and hematological findings
t(9;22) (q34;q11.2) translocation and its variants give when seeking a definitive diagnosis. [13]
rise to Philadelphia chromosome (Ph), which results
in juxtaposition of DNA sequence of BCR and ABL1 Genetic abnormalities in MDS patients include
genes, mRNA translation of this chimeric gene, and deletions, gains, and chromosomal rearrangements,
eventual dysregulated expression of oncogenic as well as molecular changes such as point mutations,
tyrosine kinase of BCR-ABL1 fusion, which seems to epigenetic changes, and dysregulated miRNAs. [13]
be sufficient to initiate the leukemogenesis process. Conventional cytogenetics and fluorescent in situ
[6]
Three different forms of BCR-ABL1 fusion protein are hybridization (FISH) analysis are commonly used
produced based on the breakpoint site in the BCR gene: methods for detection of karyotype abnormalities;
p190, p210, and p230. Although they are all associated both methods have advantages and disadvantages.
with development of leukemia, these three forms have Karyotype commonly evaluates 20 metaphase cells.
different clinical outcomes. Although BCR-ABL1 FISH analysis can detect chromosomal abnormalities
[7]
chromosomal abnormality is pathognomic for chronic with a higher resolution, but it is limited to regions with
[14]
myeloid leukemia (CML), it is observed de novo in predefined probes. Therefore, it seems prudent to
B-cell precursor acute lymphoblastic leukemia (ALL), perform initial assessment by conventional karyotyping
especially in adults, as well as in 0.48-3% of patients and to use FISH analysis for further investigations.
with AML. [8,9] In contrast, Ph is extremely rare in MDS Several studies have shown that FISH analysis in
patients and shows up in the last stages of disease, conjunction with karyotyping can provide further
so it is associated with leukemic transformation in information, especially in cases where the karyotype
most cases. Although few cases of Ph MDS have appearsnormal. [15,16] Chromosomal abnormalities have
[10]
+
been reported, diagnosis of this disorder is especially been detected in approximately 50% of patients with
important, since these patients show a poor response de novo MDS and in more than 80% of MDS cases
to conventional therapeutic approaches. [11] secondary to chemotherapy and toxic agents. In a large-
scale study on 2124 MDS patients, 48% had normal
The presence of common traits in MDS and karyotype and 52% showed abnormal karyotype. The
myeloproliferative disease (MPD) suggests that some most common cytogenetic abnormality was del 5q in
genetic abnormalities associated with MPD are most 30% of patients, followed by -7/del 7q in 21%, and +8 in
likely involved in the development or progression of 16% of cases. Detection of cytogenetic abnormalities
[17]
MDS. Lack of knowledge about the importance of this plays a significant role in disease prognosis, so it has
abnormality in MDS patients may lead to inaccurate been recognized as a marker in all the prognostic
assessment of BCR-ABL fusion and choice of an systems, including international prognostic scoring
inappropriate therapeutic protocol. Therefore, besides system (IPSS), revised-international prognostic
studying the reported cases, this review aims to scoring system (IPSS-R), and WPSS. IPSS-R isone
investigate the typical features of Ph MDS patients of the most widely used prognostic systems for MDS
+
and will assess the role of genetic abnormalities, patients. In this classification system, -Y and del
[18]
especially the impact of BCR-ABL fusion, on response (11q) have a very good prognosis; normal karyotype,
to treatment in MDS patients. del (5q), del (12p), del (20q), and double including
del (5q) have good prognosis; del (7q), +8, +19, and
CYTOGENETIC AND MOLECULAR MARKERS i (17q) a moderate prognosis; -7, inv (3)/t (3q), double
including -7/del (7q), complex 3 abnormalities have
All classification and prognosis systems of MDS in poor prognosis; and finally patients with karyotype
recent decades have been based on cytomorphological of complex with > 3 abnormalities have a very poor
findings in PB and BM, including May-Grünwald- prognosis. [19]
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ February 28, 2017 39