Single Nucleotide Polymorphism Array-Based Karyotyping in Acute Myeloid Leukemia or Myelodysplastic Syndrome with Trisomy 8 as the Sole Chromosomal Abnormality

Abstract

The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1–q29 and 11q13.1–q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3–p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25–67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH.

Analysis of Acute Myeloid Leukemia in Korean Patients with Sole Trisomy 6

“…We reported three Korean patients with AML with a particular genetic abnormality, showing the presence of trisomy 6 as the sole clonal cytogenetic abnormality of BM cells and reviewed other cases of AML with trisomy 6 in the literature. Although other studies and literature reviews that have attempted to establish the clinicopathologic and clinicohematologic characteristics of AML with sole trisomies 4, 8, 11, and 21 [ 6 , 7 , 8 , 9 ] were found, we could not identify any correlation between morphology or prognosis and trisomy 6. In view of the literature, we suggest that trisomy 6 is a nonrandom clonal cytogenetic marker of AML, and it may sometimes be the result of transformation from other myeloid disorders.…”

Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance

“…[10][11][12][13][14][15][16] Furthermore, copyneutral loss-of-heterozygosity (LOH) (also known as uniparental disomy) detected by single-nucleotide polymorphism array has been shown to have prognostic significance in MDS. [17][18][19][20][21][22][23][24][25][26][27] In samples with unsuccessful conventional cytogenetic results, or in specimens that are not amenable to routine cytogenetics, the detection rate of genomic aberrations by single-nucleotide polymorphism microarray is particularly useful. 28,29 The majority of microarray studies in MDS rely on annotated series of patients with known diagnoses.…”

“…28,29 The majority of microarray studies in MDS rely on annotated series of patients with known diagnoses. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] To our knowledge, the diagnostic utility of microarray has not been evaluated in an unselected cohort of patients undergoing evaluation of peripheral cytopenias, nor has it been evaluated in patients who may be best categorized as having 'idiopathic cytopenias of undetermined significance'. In this study we used combined array to detect copy-neutral LOH and cryptic CNV in the marrow of patients irrespective of diagnosis who were undergoing primary bone marrow evaluation for peripheral cytopenia(s) and/or clinical concern for MDS.…”

Techniques for detecting chromosomal aberrations in myelodysplastic syndromes

“…Second, SNP-A doesn’t require live proliferating cells, hence it can still yield diagnostic information when routine cytogenetic methods are not feasible. Third, cryptic UPD with preserved chromosomal bandings can also be detected by SNP-A [ 101 ].…”