ETV6–ABL1 fusion combined with monosomy 7 in childhood B-precursor acute lymphoblastic leukemia

• Published in: International journal of hematology 2018-05, Vol.107 (5), p.604-609
• Main Authors: Uemura, Suguru, Nishimura, Noriyuki, Hasegawa, Daiichiro, Shono, Akemi, Sakaguchi, Kimiyoshi, Matsumoto, Hisayuki, Nakamachi, Yuji, Saegusa, Jun, Yokoi, Takehito, Tahara, Teppei, Tamura, Akihiro, Yamamoto, Nobuyuki, Saito, Atsuro, Kozaki, Aiko, Kishimoto, Kenji, Ishida, Toshiaki, Nino, Nanako, Takafuji, Satoru, Mori, Takeshi, Iijima, Kazumoto, Kosaka, Yoshiyuki
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Adolescent; Bone marrow; Case Report; CD19 antigen; CD20 antigen; CD34 antigen; Chemotherapy; Childhood; Children; Chromosome aberrations; Chromosome Deletion; Chromosomes, Human, Pair 7 - genetics; Dasatinib - pharmacology; Dasatinib - therapeutic use; ETS Translocation Variant 6 Protein; Female; Fever; Gene expression; Gene Fusion; Gene Rearrangement - genetics; Hematology; Humans; Imatinib; Imatinib Mesylate - pharmacology; Imatinib Mesylate - therapeutic use; Induction Chemotherapy; Leukemia; Leukemia, B-Cell - genetics; Lymphatic leukemia; Lymphocytes B; Maintenance Chemotherapy; Medicine; Medicine & Public Health; Monosomy; Oncogene Proteins v-abl - genetics; Oncogene Proteins, Fusion - genetics; Oncology; Polymerase chain reaction; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins c-ets - genetics; Remission; Remission Induction; Repressor Proteins - genetics; Transcription; Tyrosine
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-017-2371-5

ETV6–ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established chromosomal abnormality, and is associated with poor outcome. In ETV6 – ABL1 -positive cases, an in-frame fusion produced by a complex rearrangement results in constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14-year-old female BCP-ALL patient with ETV6–ABL1 fusion combined with monosomy 7. She was admitted to our hospital because of persistent fever. Bone marrow nuclear cell count on admission was 855,000/µL with 90.0% blastic cells of lymphoid morphology. Blasts were positive for CD10, CD19, CD20, CD34, cyCD79a, cyTdT, HLA-DR, and CD66c, had a karyotype of 45, XX, − 7 [18/20] and a split signal for ABL1 FISH probe (92.7%), and were sensitive to tyrosine kinase inhibitors, imatinib and dasatinib, in vitro. ETV6 – ABL1 fusion transcript was identified by whole transcriptome sequencing and confirmed by RT-PCR. She was treated with the high-risk protocol based on ALL-BFM 95, achieved complete remission (CR) after induction chemotherapy, and maintained CR for 4 months. To our knowledge, this is the first report of ETV6–ABL1 fusion combined with monosomy 7 in childhood BCP-ALL.