WNT inhibitory factor 1 (WIF1) is a novel fusion partner of RUNX family transcription factor 1 (RUNX1) in acute myeloid leukemia with t(12;21)(q14;q22).

As a member of the core transcription factor family, RUNX1 plays an important role in stem cell differentiation. RUNX1 rearrangements are common in myeloid and lymphoid tumors [1]. (Blood 129(15):2070-2082, 2017). One of the most commonly detected abnormalities in acute myeloid leukemia (AML) is the translocation t(8;21)(q22;q22) (Blood Adv 4(1):229-238, 2020), resulting in a RUNX1::RUNX1T1 fusion. Occasionally, RUNX1 is translocated with other genes. This article describes an AML patient with a specific chromosomal translocation involving the RUNX1 gene and the identification of the RUNX1::WIF1 fusion. Chromosomal abnormalities were detected through karyotype analysis, break gene involved was identified via fluorescence in situ hybridization (FISH), and the novel fusion was identified through transcriptome sequencing and subsequently confirmed through reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing. A 79-year-old female patient diagnosed with AML was found to have a t(12;21)(q14;q12) translocation. FISH analysis provided evidence of RUNX1 gene rearrangement. Additionally, transcriptomic sequencing revealed a novel fusion known as RUNX1::WIF1, which consists of RUNX1 exon 2 and WIF1 exon 3. The novel fusion was further confirmed through RT-PCR and Sanger sequencing. We identified WIF1 as a novel fusion partner of RUNX1 in AML. Additionally, this is the first report of a RUNX1 fusion gene with the break point in intron 2, resulting in an out-of-frame fusion. Further research is needed to investigate the impact of this novel fusion on the establishment and progression of the disease.

RUNX1 rearrangement in mature B-cell acute lymphoblastic leukemia with non-L3 morphology.

Mature B-cell acute lymphoblastic leukemia (ALL) is defined by the expression of light chain-restricted surface immunoglobulin (sIg) and usually has features of the leukemic phase of Burkitt lymphoma including FAB-L3 morphology and MYC rearrangement. Recently, another distinct entity in childhood mature B-cell ALL has been characterized as non-L3 morphology and KMT2A rearrangement. Here we report an unusual case of mature B-cell ALL that presented with RUNX1 rearrangement. A 65-year-old male was admitted to our department for thorough examination of leukocytosis and thrombocytopenia. The patient's bone marrow was hypercellular and infiltrated with 97.8% myeloperoxidase-negative, medium-to-large-sized blasts without cytoplasmic vacuoles. Immunophenotypes were characterized by the presence of light chain-restricted sIg and the lack of immature markers, indicating a diagnosis of mature B-cell ALL with L2 morphology: sIg-κ+, CD19+, CD20+, CD22+, CD79a+, TdT-, and CD34-. G-banding combined with spectral karyotyping showed the following complex karyotype: 45,X,der(Y;10)(p10;q10),del(13)(q?),inv(21)(p13q22.1). Fluorescence in situ hybridization revealed separated signals of RUNX1 at 21q22.1, whereas rearrangements of MYC and KMT2A were not found. To our knowledge, inv(21)(p13q22.1) involving RUNX1 is a novel cytogenetic aberration and this is the first case of mature B-cell ALL that presented with RUNX1 rearrangement. Thus, RUNX1 may be implicated in the pathogenesis of mature B-cell ALL showing non-L3 morphology without MYC rearrangement.

[Efficacy and prognostic factors of the chemotherapy regimen of CCLG-ALL-2008 on pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement].

Objective: To evaluate the predictive role of ETV6-RUNX1 fusion gene in protocol CCLG-ALL-2008 as well as identify the prognostic factors that influence the outcome of ALL with ETV6-RUNX1 fusion gene. Methods: One hundred and seventy-eight patients newly diagnosed with pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement from April 2008 to April 2015 were enrolled in CCLG-ALL-2008. The follow up period ended in July 2018; we performed retrospective analyses of their data to determine the efficacy of the regimen and the prognostic factors. Results: The median age of the study population (178 pediatric patients) , including 100 boys and 78 girls was 4 (1-13) y, and the median white blood cell count at diagnosis was 9.46 (1.25-239.83) ×10(9)/L. Three patients died, and 1 was lost to follow up by the end of the first induction chemotherapy, resulting in an induced remission rate of 97.8% (174/178) . The cumulative incidence of relapse was 15.9% with a median follow up of 73.5 mon. Total 83.3% of the relapse cases were those of isolated bone marrow relapse, while 79.2% of the cases were those of late relapse. The median interval time between relapse and first complete remission was 35.5 mon (range, 1-62 months) . One of the 5 patients with early recurrence and 7 of the 19 with late recurrence cases survived. The 5-year-OS and 5-year-EFS of ETV6-RUNX1 positive children was (89.4±2.4) % and (82.1±6.9) %, respectively. The estimated 10-year-OS and 10-year-EFS of ETV6-RUNX1 positive children was (88.6±2.5) % and (77.3±4.0) %, respectively. The Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. Univariate statistical analysis showed that poor prognostic factors that influenced survival included central nervous system state 2 at diagnosis, poor prednisone response, high risk, gene positivity after induction chemotherapy, as well as MRD positivity and gene positivity at the 12(th) week. In the multivariate analysis, only the central nervous system state 2 at diagnosis and MRD positivity at the 12(th) week were associated with the outcome. Conclusion: ETV6-RUNX1-positive ALL is a subgroup with a favorable prognosis as per the CCLG-ALL-2008 protocol. Patients with ETV6-RUNX1 should be given more intensive therapy, including hematopoietic stem cell transplantation when they are CNS2 at diagnosis or have high level of MRD at the 12(th) week after treatment.