Publication Date:
2018-11-29
Description:
Background. In 2016 WHO classification of myeloid neoplasms and acute leukemias a new provisional entity 'B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like' has been introduced. Two current strategies of BCR-ABL1-like ALL detection are based on gene expression profile revealed either by microarray ('BCR-ABL-like') or by NGS / patented TaqMan low-density array (TLDA) ('Ph-like'). Although both techniques and not widely applicable. Aims. To find out whether expression profile based on combined expression data of 5 genes assessed by real-time PCR can be used for the identification of BCR-ABL1-like pediatric ALL patients. Methods. The study was done on initial bone marrow samples of 147 primary pediatric BCP-ALL patients. Positive cohort included 10 BCR-ABL1-positive ALL patients, negative cohort consisted of 59 cases with known structural or numerical aberrations. Among them there were 21 patients with high hyperdiploidy, 1 low hypodploid, 1 near tetraploid and 1 iAMP21 cases, 23 patients with translocation t(12;21)(p13;q22), 5 cases with t(1;19)(q23;p13), 1 case with t(9;11)(p22;q23) and 6 Down syndrome (DS-ALL) patients. The rest 78 cases were called 'B-others' ALL and designated as training cohort. According to the previously published data (R. Harvey et al. ASH 2013 abs #826.) we picked 5 genes (IGJ, SPATS2L, MUC4, CRLF2, CA6) those expressions were estimated by real-time PCR. ΔCt method was applied in relation to ABL1 expression. In case of having expression results similar to BCR-ABL1-positive cases, patients with BCR-ABL1-negative ALL were attributed as BCR-ABL1-like ALL. In 113 patients we evaluated IKZF1 status by MLPA using P335 kit (MRC-Holland). Presence of ABL1, ABL2, CRLF2, IgH, JAK2, PDGFRb/CSFR1 gene rearrangements were done by FISH. Prognostic significance of BCR-ABL-like profile was estimated in 66 'B-others' patients uniformly treated according to the ALL-MB 2008 protocol. Informed consent was obtained in all cases. Results. Hierarchical cluster analysis and principal component analysis showed that 16 examined samples were clustered together with 9 BCR-ABL1-positive ones. Among them there were 3 DS patients, 1 iAMP21, 1 t(12;21) cases and 11 patients from 'B-other' group. IKZF1 deletions and high CRLF2 expression were more frequent in BCR-ABL1-like group in comparison to non-BCR-ABL1-like (67% vs 11%, and 40% vs 6%, correspondingly; p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink