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

T. Imamura, N. Kiyokawa, M. Kato, C. Imai, Y. Okamoto, M. Yano, K. Ohki, Y. Yamashita, Y. Kodama, A. Saito, M. Mori, S. Ishimaru, T. Deguchi, Y. Hashii, Y. Shimomura, T. Hori, K. Kato, H. Goto, C. Ogawa, K. Koh & 11 others T. Taki, A. Manabe, A. Sato, A. Kikuta, S. Adachi, K. Horibe, A. Ohara, A. Watanabe, Y. Kawano, E. Ishii, Hiroyuki Shimada

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Abstract

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.

Original languageEnglish
Pages (from-to)e419
JournalBlood Cancer Journal
Volume6
DOIs
Publication statusPublished - 2016 May 13

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B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Japan
Phosphotransferases
Pediatrics
Platelet-Derived Growth Factor beta Receptor
Age of Onset
Protein-Tyrosine Kinases
Cytokine Receptors
National Cancer Institute (U.S.)
Multiplex Polymerase Chain Reaction
Hematopoietic Stem Cell Transplantation
Residual Neoplasm
Receptor Protein-Tyrosine Kinases
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
Leukocyte Count
Disease-Free Survival
Survival Rate
Drug Therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan. / Imamura, T.; Kiyokawa, N.; Kato, M.; Imai, C.; Okamoto, Y.; Yano, M.; Ohki, K.; Yamashita, Y.; Kodama, Y.; Saito, A.; Mori, M.; Ishimaru, S.; Deguchi, T.; Hashii, Y.; Shimomura, Y.; Hori, T.; Kato, K.; Goto, H.; Ogawa, C.; Koh, K.; Taki, T.; Manabe, A.; Sato, A.; Kikuta, A.; Adachi, S.; Horibe, K.; Ohara, A.; Watanabe, A.; Kawano, Y.; Ishii, E.; Shimada, Hiroyuki.

In: Blood Cancer Journal, Vol. 6, 13.05.2016, p. e419.

Research output: Contribution to journalArticle

Imamura, T, Kiyokawa, N, Kato, M, Imai, C, Okamoto, Y, Yano, M, Ohki, K, Yamashita, Y, Kodama, Y, Saito, A, Mori, M, Ishimaru, S, Deguchi, T, Hashii, Y, Shimomura, Y, Hori, T, Kato, K, Goto, H, Ogawa, C, Koh, K, Taki, T, Manabe, A, Sato, A, Kikuta, A, Adachi, S, Horibe, K, Ohara, A, Watanabe, A, Kawano, Y, Ishii, E & Shimada, H 2016, 'Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan', Blood Cancer Journal, vol. 6, pp. e419. https://doi.org/10.1038/bcj.2016.28
Imamura, T. ; Kiyokawa, N. ; Kato, M. ; Imai, C. ; Okamoto, Y. ; Yano, M. ; Ohki, K. ; Yamashita, Y. ; Kodama, Y. ; Saito, A. ; Mori, M. ; Ishimaru, S. ; Deguchi, T. ; Hashii, Y. ; Shimomura, Y. ; Hori, T. ; Kato, K. ; Goto, H. ; Ogawa, C. ; Koh, K. ; Taki, T. ; Manabe, A. ; Sato, A. ; Kikuta, A. ; Adachi, S. ; Horibe, K. ; Ohara, A. ; Watanabe, A. ; Kawano, Y. ; Ishii, E. ; Shimada, Hiroyuki. / Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan. In: Blood Cancer Journal. 2016 ; Vol. 6. pp. e419.
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abstract = "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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AU - Imamura, T.

AU - Kiyokawa, N.

AU - Kato, M.

AU - Imai, C.

AU - Okamoto, Y.

AU - Yano, M.

AU - Ohki, K.

AU - Yamashita, Y.

AU - Kodama, Y.

AU - Saito, A.

AU - Mori, M.

AU - Ishimaru, S.

AU - Deguchi, T.

AU - Hashii, Y.

AU - Shimomura, Y.

AU - Hori, T.

AU - Kato, K.

AU - Goto, H.

AU - Ogawa, C.

AU - Koh, K.

AU - Taki, T.

AU - Manabe, A.

AU - Sato, A.

AU - Kikuta, A.

AU - Adachi, S.

AU - Horibe, K.

AU - Ohara, A.

AU - Watanabe, A.

AU - Kawano, Y.

AU - Ishii, E.

AU - Shimada, Hiroyuki

PY - 2016/5/13

Y1 - 2016/5/13

N2 - 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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