Skip to main content

Conference Program

Subpage Hero

Loading

RUNX1::SLTM – a new fusion gene developed from t(15;21)(q22;q22) during accelerated phase in CML

Cancer Genetics and Therapeutics
  • Primary Categories:
    • Cancer
  • Secondary Categories:
    • Cancer
Introduction
Downregulation of RUNX1due to fusion with RUNX1T1or with MECOM is a recurring leukemogenic abnormality in myeloid neoplasia, whereas ETV6::RUNX1 is characteristic of pre-B-ALL. Native RUNX1 is involved in regulation of genes involved in hematopoiesis, cell cycle regulation and several other cellular pathways. Several unique fusion partners of RUNX1 have been reported in hematopoietic neoplasia cases. Here we report on a new fusion partner of RUNX1 that developed in a CML patient at accelerated phase and failed to achive remission.

 

Case Presentation
The patient is a 46-year-old female with a history of a skin lesion positive for BRAF::STRN3 18 months before to the diagnosis of the current hematologic neoplasm. At presentation the patient had 0.11% myeloblasts that were CD34+, and CD56+ (partial), and failed to achieve MMR with any line of therapy. 

 

Diagnostic Workup
Bone marrow (left iliac crest) evaluation showed hypercellular marrow with trilineage hematopoiesis and left-shifted myeloidhyperplasia, and had 0.6% blasts; a diagnosis of myeloproliferative neoplasms was rendred. Karyotype was 46,XX,t(9;22)(q34;q11.2)[20] with BCR::ABL1 positive in 85.5% cells by FISH. NGS analysis of the BM specimen at this time was positive for BCR::ABL1, RT-PCR analysis detected BCR::ABL1  with a transcript of e13/e14-a2 and had other single nucleotide variants – PTPRD c.5239C>T p.R1747c and KIT c.200C>G  pT67S.. Chromosome analysis at the time of disease progression showed 47,XX,+8,t(9;22)(q34;q11.2),t(15;22)(q22;q22)[7]/46,XX[13]. In addition to detecting BCR::ABL1, RUNX1 FISH probe detected rearrangement in interphase nuclei, and on de-banded metaphases rearranged RUNX1 signal was mapped to 15q22. RNASeq analysis of this specimen detected RUNX1::SLTM with a translocation break in RUNX1 (NM_001764, chr21:36206707) at the end of exon 7 and  in SLTM (NM_024755, chr15:59189432) at the start of exon 10; this has not been reported previously. In addition, an ABL1 missense variant p.G250E was also detected at this time.  

Treatment and Management
Patient was treated with imatinib, dasatinib, and bosutinib with failure to achieve MMR with any line of therapy and showed rising BCR/ABL1 transcripts. She had progression with an increased peripheral blood blast count (10%)  which was detected at 28 months after diagnosis.

Outcome and Follow-Up
Patient is alive at the time of last followup with persistent dieases.

Discussion
There have been three reports on the concurrent presence of t(15;21)(q22;q22) along with a t(9;22)(q34;q11.2) in CML patients at diagnosis or with development at blast crisis. These three patients were treated with TKIs; but the translocation was not further characterized.

Conclusion
This protends an aggressive disease biology and novel therapeutics like targeted agents and cellular therapies like CAR T-cells are being explored. SLTM is a member of the scaffold attachment factor B (SAFB) family that play crucial roles in DNA repair, processing of mRNA and regulatory RNA and interaction with chromatin modifying complexes (Norman et al 2016). Although several SNP variants in this gene were documented in different B-cell neoplasms fusion with other genes has not been reported. Molecular characterization of identical translocation is warranted to understand its tumorigenic etiology.

Agenda

Sponsors