IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia

Yuka Yamashita, Akira Shimada, Tomomi Yamada, Kazutaka Yamaji, Toshinori Hori, Masahito Tsurusawa, Arata Watanabe, Atsushi Kikuta, Keiko Asami, Akiko M. Saito, Keizo Horibe

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Abstract

Background: Genome-wide analysis studies have demonstrated that IKZF1, CRLF2, and JAK2 gene alterations correlate with poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the prognostic significance for these gene alterations has not been clarified in Japanese patients. Procedure: A total of 194 patients with BCP-ALL enrolled in the Japanese Children's Cancer & Leukemia Study Group ALL 2004 clinical trial were assessed for the presence of three different gene alterations: IKZF1 deletions, CRLF2 expression and JAK2 mutation. Results: IKZF1 deletions and CRLF2-high expression were identified in 22 of 177 (12%) patients and in 15 of 141 (11%) patients, respectively. However, JAK2 R683 mutation was detected only one of 177 patients. The 4-year event-free survival (4y-EFS) was different when comparing patients with or without IKZF1 deletions (68.2% vs. 85.2%; P=0.04) and was also different when comparing patients with different CRLF2 expression levels (high, 66.7% vs. low, 88.1%; P=0.03). The differences in 4y-EFS were statistically significant in patients with ALL in the National Cancer Institute (NCI)-high risk group (HR-ALL) (IKZF1 deletions: yes, 58.3% vs. no, 87.0%, P=0.02; CRLF2 expression: high, 55.6% vs. low, 85.3%, P=0.04) but not in patients with ALL in the NCI-standard risk group (SR-ALL; IKZF1 deletions: yes, 80.0% vs. no, 84.4%, P=0.75; CRLF2 expression: high, 83.3% vs. low, 89.2%, P=0.77). Coexistence of IKZF1 deletions and CRLF2-high expression associated with poor outcomes. Conclusions: IKZF1 deletions and CRLF2-high expression predicted poor outcomes in patients with HR-ALL but not in patients with SR-ALL in our Japanese cohort. Pediatr Blood Cancer 2013;60:1587-1592.

Original languageEnglish
Pages (from-to)1587-1592
Number of pages6
JournalPediatric Blood and Cancer
Volume60
Issue number10
DOIs
Publication statusPublished - Oct 2013

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B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genes
National Cancer Institute (U.S.)
Disease-Free Survival
Mutation
Neoplasms
Leukemia
Clinical Trials
Genome
Pediatrics

Keywords

  • Acute lymphoblastic leukemia
  • CRLF2
  • IKZF1
  • JAK2

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia. / Yamashita, Yuka; Shimada, Akira; Yamada, Tomomi; Yamaji, Kazutaka; Hori, Toshinori; Tsurusawa, Masahito; Watanabe, Arata; Kikuta, Atsushi; Asami, Keiko; Saito, Akiko M.; Horibe, Keizo.

In: Pediatric Blood and Cancer, Vol. 60, No. 10, 10.2013, p. 1587-1592.

Research output: Contribution to journalArticle

Yamashita, Y, Shimada, A, Yamada, T, Yamaji, K, Hori, T, Tsurusawa, M, Watanabe, A, Kikuta, A, Asami, K, Saito, AM & Horibe, K 2013, 'IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia', Pediatric Blood and Cancer, vol. 60, no. 10, pp. 1587-1592. https://doi.org/10.1002/pbc.24571
Yamashita, Yuka ; Shimada, Akira ; Yamada, Tomomi ; Yamaji, Kazutaka ; Hori, Toshinori ; Tsurusawa, Masahito ; Watanabe, Arata ; Kikuta, Atsushi ; Asami, Keiko ; Saito, Akiko M. ; Horibe, Keizo. / IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia. In: Pediatric Blood and Cancer. 2013 ; Vol. 60, No. 10. pp. 1587-1592.
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abstract = "Background: Genome-wide analysis studies have demonstrated that IKZF1, CRLF2, and JAK2 gene alterations correlate with poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the prognostic significance for these gene alterations has not been clarified in Japanese patients. Procedure: A total of 194 patients with BCP-ALL enrolled in the Japanese Children's Cancer & Leukemia Study Group ALL 2004 clinical trial were assessed for the presence of three different gene alterations: IKZF1 deletions, CRLF2 expression and JAK2 mutation. Results: IKZF1 deletions and CRLF2-high expression were identified in 22 of 177 (12{\%}) patients and in 15 of 141 (11{\%}) patients, respectively. However, JAK2 R683 mutation was detected only one of 177 patients. The 4-year event-free survival (4y-EFS) was different when comparing patients with or without IKZF1 deletions (68.2{\%} vs. 85.2{\%}; P=0.04) and was also different when comparing patients with different CRLF2 expression levels (high, 66.7{\%} vs. low, 88.1{\%}; P=0.03). The differences in 4y-EFS were statistically significant in patients with ALL in the National Cancer Institute (NCI)-high risk group (HR-ALL) (IKZF1 deletions: yes, 58.3{\%} vs. no, 87.0{\%}, P=0.02; CRLF2 expression: high, 55.6{\%} vs. low, 85.3{\%}, P=0.04) but not in patients with ALL in the NCI-standard risk group (SR-ALL; IKZF1 deletions: yes, 80.0{\%} vs. no, 84.4{\%}, P=0.75; CRLF2 expression: high, 83.3{\%} vs. low, 89.2{\%}, P=0.77). Coexistence of IKZF1 deletions and CRLF2-high expression associated with poor outcomes. Conclusions: IKZF1 deletions and CRLF2-high expression predicted poor outcomes in patients with HR-ALL but not in patients with SR-ALL in our Japanese cohort. Pediatr Blood Cancer 2013;60:1587-1592.",
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T1 - IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia

AU - Yamashita, Yuka

AU - Shimada, Akira

AU - Yamada, Tomomi

AU - Yamaji, Kazutaka

AU - Hori, Toshinori

AU - Tsurusawa, Masahito

AU - Watanabe, Arata

AU - Kikuta, Atsushi

AU - Asami, Keiko

AU - Saito, Akiko M.

AU - Horibe, Keizo

PY - 2013/10

Y1 - 2013/10

N2 - Background: Genome-wide analysis studies have demonstrated that IKZF1, CRLF2, and JAK2 gene alterations correlate with poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the prognostic significance for these gene alterations has not been clarified in Japanese patients. Procedure: A total of 194 patients with BCP-ALL enrolled in the Japanese Children's Cancer & Leukemia Study Group ALL 2004 clinical trial were assessed for the presence of three different gene alterations: IKZF1 deletions, CRLF2 expression and JAK2 mutation. Results: IKZF1 deletions and CRLF2-high expression were identified in 22 of 177 (12%) patients and in 15 of 141 (11%) patients, respectively. However, JAK2 R683 mutation was detected only one of 177 patients. The 4-year event-free survival (4y-EFS) was different when comparing patients with or without IKZF1 deletions (68.2% vs. 85.2%; P=0.04) and was also different when comparing patients with different CRLF2 expression levels (high, 66.7% vs. low, 88.1%; P=0.03). The differences in 4y-EFS were statistically significant in patients with ALL in the National Cancer Institute (NCI)-high risk group (HR-ALL) (IKZF1 deletions: yes, 58.3% vs. no, 87.0%, P=0.02; CRLF2 expression: high, 55.6% vs. low, 85.3%, P=0.04) but not in patients with ALL in the NCI-standard risk group (SR-ALL; IKZF1 deletions: yes, 80.0% vs. no, 84.4%, P=0.75; CRLF2 expression: high, 83.3% vs. low, 89.2%, P=0.77). Coexistence of IKZF1 deletions and CRLF2-high expression associated with poor outcomes. Conclusions: IKZF1 deletions and CRLF2-high expression predicted poor outcomes in patients with HR-ALL but not in patients with SR-ALL in our Japanese cohort. Pediatr Blood Cancer 2013;60:1587-1592.

AB - Background: Genome-wide analysis studies have demonstrated that IKZF1, CRLF2, and JAK2 gene alterations correlate with poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the prognostic significance for these gene alterations has not been clarified in Japanese patients. Procedure: A total of 194 patients with BCP-ALL enrolled in the Japanese Children's Cancer & Leukemia Study Group ALL 2004 clinical trial were assessed for the presence of three different gene alterations: IKZF1 deletions, CRLF2 expression and JAK2 mutation. Results: IKZF1 deletions and CRLF2-high expression were identified in 22 of 177 (12%) patients and in 15 of 141 (11%) patients, respectively. However, JAK2 R683 mutation was detected only one of 177 patients. The 4-year event-free survival (4y-EFS) was different when comparing patients with or without IKZF1 deletions (68.2% vs. 85.2%; P=0.04) and was also different when comparing patients with different CRLF2 expression levels (high, 66.7% vs. low, 88.1%; P=0.03). The differences in 4y-EFS were statistically significant in patients with ALL in the National Cancer Institute (NCI)-high risk group (HR-ALL) (IKZF1 deletions: yes, 58.3% vs. no, 87.0%, P=0.02; CRLF2 expression: high, 55.6% vs. low, 85.3%, P=0.04) but not in patients with ALL in the NCI-standard risk group (SR-ALL; IKZF1 deletions: yes, 80.0% vs. no, 84.4%, P=0.75; CRLF2 expression: high, 83.3% vs. low, 89.2%, P=0.77). Coexistence of IKZF1 deletions and CRLF2-high expression associated with poor outcomes. Conclusions: IKZF1 deletions and CRLF2-high expression predicted poor outcomes in patients with HR-ALL but not in patients with SR-ALL in our Japanese cohort. Pediatr Blood Cancer 2013;60:1587-1592.

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KW - CRLF2

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KW - JAK2

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