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<p>In vitro models of acute leukemia are crucial for understanding its biology and developing effective treatments. The authors have established and characterized a novel cell line, ICH-BCPALL-3, which expresses the <i>TCF3::HLF</i> fusion from B cell precursor acute lymphoblastic leukemia (BCP-ALL). The karyotype of the cultured cells is 46,XY, der(1)(1qter- &gt; 1q11::1p32- &gt; 1q11::4q21- &gt; 4qter), der(4)t(1;4)(q11;p32), add(8)(q24), del(17)(q24). Analysis of the diagnostic sample revealed deletions in <i>RB1</i>, <i>VPREB1</i>, and <i>NR3C1</i>. The cell line showed additional deletions of <i>VPREB1</i>, <i>NR3C1</i>, and <i>CDKN2A</i>/<i>2B</i>, as well as a gain of <i>AKT1</i>. The loci for <i>PAX5</i> and <i>BTG1</i> were retained. Exome and Sanger sequencing identified nucleotide variants of <i>ARID5B</i> and <i>NCOR1</i> in the diagnostic sample, as well as a <i>KRAS</i> variant (p.Lys117Asn) in the first recurrent sample and another <i>KRAS</i> variant (p.Asp119Gly) in the second recurrent sample and the cell line. Transcriptome analysis and RT-PCR confirmed that all examined samples contained a <i>TCF3::HLF</i> chimeric transcript. However, molecular cytogenetics did not verify the juxtaposition of <i>TCF3</i> and <i>HLF</i> loci. Further long-range PCR analyses confirmed that genomic material containing <i>HLF</i> exon 4 was inserted into <i>TCF3</i> intron 16. Using dimensional reduction techniques, we found that the current cell line shares an expression pattern with other <i>TCF3::HLF</i>-positive BCP-ALL cell lines. The cytotoxicity assay indicated that the cell line is sensitive to Aurora Kinase B inhibitor, but not to BCL2 inhibitor. This cell line is the first <i>TCF3::HLF</i>-positive BCP-ALL model without the t(17;19) translocation, facilitating research into leukemogenesis and the development of novel treatments for patients with poor prognosis associated with <i>TCF3::HLF</i>-positive BCP-ALL.</p>

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Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF

  • 期刊论文

  • 发表日期：

    2025年11月19日

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  • Keisuke Kato,
  • Ioannis Panagopoulos,
  • Ai Yoshimi,
  • Norihito Ikenobe,
  • Chie Kobayashi,
  • Hiroaki Goto,
  • Mieko Ito,
  • Maiko Sagisaka,
  • Kristin Andersen,
  • Asami Noda,
  • Minori Tamai,
  • Koshi Akahane,
  • Takeshi Inukai,
  • Kentaro Ohki,
  • Nobutaka Kiyokawa,
  • Masahiro Tsuchida

摘要

In vitro models of acute leukemia are crucial for understanding its biology and developing effective treatments. The authors have established and characterized a novel cell line, ICH-BCPALL-3, which expresses the TCF3::HLF fusion from B cell precursor acute lymphoblastic leukemia (BCP-ALL). The karyotype of the cultured cells is 46,XY, der(1)(1qter- > 1q11::1p32- > 1q11::4q21- > 4qter), der(4)t(1;4)(q11;p32), add(8)(q24), del(17)(q24). Analysis of the diagnostic sample revealed deletions in RB1, VPREB1, and NR3C1. The cell line showed additional deletions of VPREB1, NR3C1, and CDKN2A/2B, as well as a gain of AKT1. The loci for PAX5 and BTG1 were retained. Exome and Sanger sequencing identified nucleotide variants of ARID5B and NCOR1 in the diagnostic sample, as well as a KRAS variant (p.Lys117Asn) in the first recurrent sample and another KRAS variant (p.Asp119Gly) in the second recurrent sample and the cell line. Transcriptome analysis and RT-PCR confirmed that all examined samples contained a TCF3::HLF chimeric transcript. However, molecular cytogenetics did not verify the juxtaposition of TCF3 and HLF loci. Further long-range PCR analyses confirmed that genomic material containing HLF exon 4 was inserted into TCF3 intron 16. Using dimensional reduction techniques, we found that the current cell line shares an expression pattern with other TCF3::HLF-positive BCP-ALL cell lines. The cytotoxicity assay indicated that the cell line is sensitive to Aurora Kinase B inhibitor, but not to BCL2 inhibitor. This cell line is the first TCF3::HLF-positive BCP-ALL model without the t(17;19) translocation, facilitating research into leukemogenesis and the development of novel treatments for patients with poor prognosis associated with TCF3::HLF-positive BCP-ALL.