Chromosomal microarray analysis is superior in identifying cryptic aberrations in patients with acute lymphoblastic leukemia at diagnosis/relapse as a single assay

Introduction Conventional cytogenetics (CC) is important in diagnosis, therapy, monitoring of post‐transplant bone marrow, and prognosis assessment of acute lymphoblastic leukemia (ALL). However, due to the nature of ALL, CC often encounters difficulties of complex karyotype, poor chromosome morphol...

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Published in:International journal of laboratory hematology 2019-08, Vol.41 (4), p.561-571
Main Authors: Chen, Chuanfei, Heng, Evelyn Yee Hsieh, Lim, Alvin Soon Tiong, Lau, Lai Ching, Lim, Tse Hui, Wong, Gee Chuan, Tien, Sim Leng
Format: Article
Language:English
Subjects:
a single assay
Acute lymphoblastic leukemia
Adolescent
Adult
Aged
Bone marrow
Bone marrow transplantation
Cell cycle
Chromosome Aberrations
Chromosome translocations
Chronic lymphocytic leukemia
Copy number
cryptic aberrations
Cytogenetics
Diagnosis
DNA Copy Number Variations
Female
Fluorescence in situ hybridization
Heterozygosity
Humans
Hybridization analysis
In Situ Hybridization, Fluorescence
Karyotypes
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Loss of Heterozygosity
Lymphatic leukemia
Lymphocytes B
Lymphopoiesis
Male
microarray
Middle Aged
Pax5 protein
Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Recurrence
routine
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Summary:Introduction Conventional cytogenetics (CC) is important in diagnosis, therapy, monitoring of post‐transplant bone marrow, and prognosis assessment of acute lymphoblastic leukemia (ALL). However, due to the nature of ALL, CC often encounters difficulties of complex karyotype, poor chromosome morphology, low mitotic index, or normal cells dividing only. In contrast, chromosomal microarray analysis (CMA) showed a specificity >99% and a sensitivity of 100% in chronic lymphocytic leukemia (CLL) patients. Here, we report our experience with CMA on adult ALL patients. Methods Thirty‐three bone marrow/blood samples from ALL patients (aged 18‐79 years, median 44) at diagnosis/relapse, analyzed by CC and/or fluorescence in situ hybridization (FISH), were recruited. Chromosomal microarray analysis results were compared with CC. Fluorescence in situ hybridization analysis, if available, was applied when there was a discrepancy. Results Copy‐neutral loss‐of‐heterozygosity (CN‐LOH) was found in 8 cases (24.2%). Only CN‐LOH at 9p was recurrent (3 cases, 9.1%). Copy number alterations (CNAs) were detected in 6 of 9 cases (66.7%) with normal karyotypes, in 3 of 5 cases (60.0%) with sole “balanced” translocations, and in 18 of 19 cases (94.7%) with complex karyotypes. Common CNAs involved CDKN2A/2B (30.3%), IKZF1 (27.3%), PAX5 (9.1%), RB1 (9.1%), BTG1 (6.7%), and ETV6 (6.7%), which regulate cell cycle, B lymphopoiesis, or act as tumor suppressors in ALL. Copy number alteration detection rate by CMA was 81.8% (27 of 33 cases) as compared to 57.6% (19 of 33 cases) by CC. Conclusion Incorporation of CMA as a routine clinical test at the time of diagnosis/relapse, in conjunction with CC and/or FISH, is highly recommended.
ISSN:1751-5521
1751-553X
DOI:10.1111/ijlh.13052