JAK2-mutated acute myeloid leukemia: comparison of next-generation sequencing (NGS) and single nucleotide polymorphism array (SNPa) findings between two cases

Purpose This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) –based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses. Patients and Methods A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis. Results Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020). Conclusion Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.

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High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations

Blood ◽

10.1182/blood-2011-09-380444 ◽

2012 ◽

Vol 119 (10) ◽

pp. e67-e75 ◽

Cited By ~ 45

Author(s):

Michael W. M. Kühn ◽

Ina Radtke ◽

Lars Bullinger ◽

Salil Goorha ◽

Jinjun Cheng ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Single Nucleotide Polymorphism Array ◽

Nucleotide Polymorphism ◽

Array Analysis ◽

Core Binding Factor ◽

Single Nucleotide ◽

Binding Factor ◽

Acute Myeloid

Abstract To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.

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Identifying the similarities and differences between single nucleotide polymorphism array (SNPa) analysis and karyotyping in acute myeloid leukemia and myelodysplastic syndromes

Revista Brasileira de Hematologia e Hemoterapia ◽

10.1016/j.bjhh.2014.09.011 ◽

2015 ◽

Vol 37 (1) ◽

pp. 48-54 ◽

Cited By ~ 7

Author(s):

Thiago Rodrigo de Noronha ◽

Sandra Serson Rohr ◽

Maria de Lourdes Lopes Ferrari Chauffaille

Keyword(s):

Single Nucleotide Polymorphism ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Single Nucleotide Polymorphism Array ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Similarities And Differences ◽

Acute Myeloid

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New Lesions Detected by Single Nucleotide Polymorphism Array–Based Chromosomal Analysis Have Important Clinical Impact in Acute Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2009.21.9840 ◽

2009 ◽

Vol 27 (31) ◽

pp. 5219-5226 ◽

Cited By ~ 88

Author(s):

Ramon V. Tiu ◽

Lukasz P. Gondek ◽

Christine L. O'Keefe ◽

Jungwon Huh ◽

Mikkael A. Sekeres ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Acute Myeloid Leukemia ◽

Predictive Value ◽

Myeloid Leukemia ◽

Single Nucleotide Polymorphism Array ◽

Uniparental Disomy ◽

Prognostic Impact ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Acute Myeloid

PurposeCytogenetics is the primary outcome predictor in acute myeloid leukemia (AML). Metaphase cytogenetics (MC) detects an abnormal karyotype in only half of patients with AML, however. Single nucleotide polymorphism arrays (SNP-A) can detect acquired somatic uniparental disomy (UPD) and other cryptic defects, even in samples deemed normal by MC. We hypothesized that SNP-A will improve detection of chromosomal defects in AML and that this would enhance the prognostic value of MC.Patients and MethodsWe performed 250K and 6.0 SNP-A analyses on 140 patients with primary (p) and secondary (s) AML and correlated the results with clinical outcomes and Flt-3/nucleophosmin (NPM-1) status.ResultsSNP-A is more sensitive than MC in detecting unbalanced lesions (pAML, 65% v 39%, P = .002; and sAML, 78% v 51%, P = .003). Acquired somatic UPD, not detectable by MC, was common in our AML cohort (29% in pAML and 35% in sAML). Patients with SNP-A lesions including acquired somatic UPD exhibited worse overall survival (OS) and event-free survival (EFS) in pAML with normal MC and in pAML/sAML with abnormal MC. SNP-A improved the predictive value of Flt-3 internal tandem duplication/NPM-1 status, with inferior survival seen in patients with additional SNP-A defects. Multivariate analyses confirmed the independent predictive value of SNP-A defects for OS (hazard ratio [HR] = 2.52; 95% CI, 1.29 to 5.22; P = .006) and EFS (HR = 1.72; 95% CI, 1.12 to 3.48; P = .04).ConclusionSNP-A analysis allows enhanced detection of chromosomal abnormalities and provides important prognostic impact in AML.

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