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Paridar et al. BCR-ABL and myelodysplastic syndrome

Technological advances in the field of genetic analysis, fusion was most prevalent in RAEB subgroup; 54.6%
including high-through put next-generation sequencing of cases (including 27.3% RAEB, 9.1% RAEB2, and
(HT-NGS), led to the discovery of several genetic 18.2% of RAEBt) were classified in this subgroup,
mutations in MDS patients. Studies have shown followed by RA in 13.6% of cases. This finding was in
[20]
that approximately 83% of MDS patients show genetic contrast to some extensive studies of the epidemiology
mutations. In Table 1, some of the most common of different subtypes of MDS, which indicate that RA,
[21]
mutant genes in MDS patients are summarized. RARS, RAEB, and RAEBt are the most common
subtypes, respectively. [17,36] There was a relatively poor
Although these mutations involve a range of genes, prognosis in these patients. Only 5 patients responded
their use as a diagnostic marker for MDS patients is to treatment, among which 2 cases were treated with
difficult. A good diagnostic marker must have a high imatinib. [11,13] Forty-five percent (n = 10) of patients
incidence in patients as well as an acceptable level progressed to AML, among whom 3 patients showed
of specificity, but none of these genes has a high P190 variant, 3 patients showed P210, and 1 patient
prevalence in MDS patients (low frequency), and no showed both variants [Table 2]. Only one patient
mutant gene has been specifically reported for MDS. [34] showing P190 variant progressed to ALL. Three
Mutations have been partially assessed as prognostic patients progressed to CML for whom unfortunately no
markers and have generally been associated with poor molecular study was conducted. [4,9,13]
prognosis. Therefore, although these mutations
[14]
seem to be good prognostic factors, prognostic DISCUSSION AND FUTURE PROSPECTIVE
systems have not yet taken advantage of them in their
classifications. [18] Using current advances in molecular diagnosis,
several genetic factors have been identified in MDS
DIAGNOSIS AND PROGNOSIS patients with occasional diagnostic, prognostic,
and therapeutic value. Ph chromosome is a factor
According to search of MEDLINE database, there have intermittently reported in some cases of MDS. Given
been 22 cases of MDS patients harboring BCR-ABL1 the pathognomic role of Ph in other hematologic
chromosome abnormality. There were 15 male and 7 neoplasms, it is assumed that in case of high incidence
female patients that were classified into two groups: of Ph in MDS patients, an MDS subgroup known as
adults with an average age of 64.5 years and children Ph MDS can be introduced. However, the importance
+
with an average age of 25 months. Mean hemoglobin of this genetic abnormality in MDS patients has not
concentration was 8.4 g/dL (94.7% had hemoglobin been extensively studied in MDS patients up to the
levels less than 11.5 g/dL, i.e. were anemic). Mean present time.
white blood cell count was 6.7 × 10 /mL and mean
6
platelet count was 135 × 10 /mL (61.1% had platelet The fact that only 22 cases of Ph MDS have been
+
3
counts lower than 100 × 10 ). Karyotype analysis in 20 reported to date is not conclusive evidence of low
3
cases revealed t (9:22) translocation, but in two other prevalence of this fusion in MDS patients. We state
cases, FISH test indicated the presence of Phfusion this for two reasons: (1) retrospective studies are
despite normal karyotype. [11,35] Molecular analysis inefficient for these patients because of the lack of
was done in only 10 cases; of these 5 represented careful examination of BCR-ABL fusion, and (2) no
Ph P190 variant, 4 cases had Ph210, and 1 case had study up to the present time has specifically examined
both variants [Table 2]. According to these findings, Ph this fusion in MDS patients. Given that in some cases

Table 1: The most common mutations in myelodysplastic syndromes
Mutated gene Prevalence (%) Prognosis Ref.
SF3B1 16 Favorable
RNA splicing SRSF2 13 Poor [22,23]
U2AF1 10 Poor
TET2 23 Favorable [24]
DNA methylation DNMT3A 9 Poor [25]
IDH1/2 7.5 Poor [26]
ASXL1 20 Poor [27]
Chromatin modification
EZH2 6 Poor [28]
Tp53 9.4 Poor [29]
Oncogenes Ras 15 Poor [30]
EVI1 1-2 Poor [31]
RUNX1 12 Poor [32]
Others
JAK2 53 in RARS-T Not studied [33]
40 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ February 28, 2017