Poor responses to tyrosine kinase inhibitors in a child with precursor <scp>B</scp>‐cell acute lymphoblastic leukemia with <i><scp>SNX</scp>2‐<scp>ABL</scp>1</i> chimeric transcript

Masuzawa, Aki; Kiyotani, Chikako; Osumi, Tomoo; Shibata, Yoko; Iijima, Kazutoshi; Tomita, Osamu; Nakabayashi, Kazuhiko; Oboki, Keisuke; Yasuda, Kazuki; Sanada, Hiromi; Ichikawa, Hitoshi; Hata, Kenichiro; Yoshida, Teruhiko; Matsumoto, Kenji; Kiyokawa, Nobutaka; Mori, Tetsuya

doi:10.1111/ejh.12234

Cited by 26 publications

(21 citation statements)

References 19 publications

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“…mRNA-seq was performed in 92 patients in the TCCSG cohort and 17 patients in the JACLS cohort (total 109 patients) according to previously described methods. 16 Briefly, the cDNA libraries were loaded on to the cBot (Illumina, Inc., San Diego, CA, USA) for clustering on a flow cell and then sequenced using a HiSeq1000 (Illumina). A paired-end run was performed using the SBS Kit (Illumina).…”

Section: Methodsmentioning

confidence: 99%

“…mRT-PCR was used in 264 patients (68 in the TCCSG cohort, 95 in the JACLS cohort, 83 in the CCLSG cohort and 18 in the KYCCSG cohort) to determine the presence of 15 kinase fusions, including ZMIZ1-ABL1 , SNX2-ABL1 , FOXP1-ABL1 , SFPO-ABL1 , EML1-ABL1 , NUP214-ABL1 , RCSD1-ABL1 , ETV6-ABL1 , RANBP2-ABL1 , STRN3-JAK2 , BCR-JAK2 , PAX5-JAK2 , EBF1-PDGFRB , ATF7IP-PDGFRB and P2RY8-CRLF2 . 6 , 16 , 18 The primers used in this study are listed in Supplementary Table S1 . 6 The consort diagram of the genetic analysis is described in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

“…Gene expression profiles of the patients' samples analyzed by mRNA-seq were obtained as previously described. 16 To assess similarity of gene expression profile between the kinase fusion-positive cases and the signature of BCR-ABL1 -positive cases, gene set enrichment analysis was performed as previously described. 16 …”

Section: Methodsmentioning

confidence: 99%

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Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

Imamura

Kiyokawa

Kato

et al. 2016

Blood Cancer Journal

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Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase–PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/μl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

Imamura

Kiyokawa

Kato

et al. 2016

Blood Cancer Journal

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“…MLPA analysis revealed that 34 of 278 (12·2%) patients harboured the IKZF1 deletion. To identify putative kinase fusion transcripts cooperating with IKZF1 deletion, mRNA sequencing was performed in the 16 patients for whom sufficient RNA was available, as described previously (Masuzawa et al , ). The putative transcripts were validated by reverse transcription polymerase chain reaction (RT‐PCR) and Sanger sequencing.…”

Section: Methodsmentioning

confidence: 99%

Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia withIKZF1deletion

et al. 2015

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SummaryActivating tyrosine kinase mutations or cytokine receptor signalling alterations have attracted attention as therapeutic targets for high-risk paediatric acute lymphoblastic leukaemia (ALL). We identified two novel kinase fusions, OFD1-JAK2 and NCOR1-LYN, in paediatric ALL patients with IKZF1 deletion, by mRNA sequencing. The patient with CSF2RA-CRLF2 also harboured IGH-EPOR. All these patients had high-risk features, such as high initial white blood cell counts and initial poor response to prednisolone. The functional analysis of these novel fusions is on-going to determine whether these genetic alterations can be targeted by drugs.

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“…For the determination of unrevealed genetic alterations causing CRLF2 OE, mRNA‐seq was performed in seven CRLF2 OE patients harboring IKZF1 deletions, where sufficient RNA samples were available, according to previously described methods (Masuzawa et al, ).…”

Section: Methodsmentioning

confidence: 99%

An overall characterization of pediatric acute lymphoblastic leukemia with CRLF2 overexpression

Mio

Imamura

Asai

et al. 2014

Genes Chromosomes & Cancer

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For an overall characterization of pediatric B-cell precursor acute lymphoblastic leukemia (BCPALL) with CRLF2 overexpression (OE), we conducted genetic analysis of CRLF2 in 167 pediatric BCPALL patients. CRLF2 OE was detected in 30 (18%) of 167 patients, the P2RY8-CRLF2 fusion was identified in only 3 (1.8%) of 167 patients, all of which demonstrated CRLF2 OE. Moreover, CRLF2 gain was identified in 18 (11%) of 167 patients. Messenger RNA sequencing revealed a novel fusion transcript, CSF2RA-CRLF2, in a case with CRLF2 OE, suggesting that this fusion is associated with CRLF2 OE. In survival analysis, no significant differences in 5-year event-free survival (EFS) and overall survival were observed between patients with and without CRLF2 OE (70.7 vs. 75.4%, log rank P = 0.68 and 96.4 vs. 82.1%, log rank P = 0.11, respectively). However, a significant difference in 5-year EFS between CRLF2 OE patients with and without IKZF1 deletion was observed (44.4 vs. 83.1%, log rank P = 0.02). In multivariate analysis, only IKZF1 deletion was a significant predictor of inferior OS (hazard ratio: 2.427, P = 0.04).These findings suggest that CRLF2 OE is not an independent prognostic factor in pediatric BCPALL.

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Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

Cited by 26 publications

References 19 publications

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia withIKZF1deletion

An overall characterization of pediatric acute lymphoblastic leukemia with CRLF2 overexpression

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