Bruton's Tyrosine Kinase (BTK) Is a Novel KMT2A Partner Gene
Abstract
Histone-lysine N-methyltransferase 2A gene (KMT2A) rearrangements are common genetic events in acute leukemia. They more frequent in infants and are found in 30-45% of acute myeloid leukemias (AML). They demonstrate great molecular heterogeneity with more than 90 partner genes and multiple KMT2A breakpoints involved (Meyer et al., 2018). These characteristics challenge both initial molecular diagnostics and MRD monitoring in ALs with KMT2A rearranged. As the accurate detection of all KMT2A-r types is crucial in order to correct patients' therapy and risk groups' definition, we aim to fully characterize KMT2A rearrangements within our cohort of patients using various techniques. Our recent study demonstrates a novel KMT2A partner gene - Bruton's tyrosine kinase (BTK), in a case of childhood AML.
The patient is 9 m.o. girl who presented with WBC 69,3*109/L and hepatosplenomegaly. Morphological, immunochemical and immunological examination revealed acute monocytic leukemia. Bone marrow aspirates were analyzed by G-banded karyotyping, FISH with KMT2A breakapart probe. The karyotype was 45,X,der(X?)t(X;11)(q22.1;q23.3),del(11)(q14),-20[7] with 95% KMT2A-rearranged nuclei. Real-time RT-PCR for 8 most common KMT2A rearrangements screening was negative. Targeted RNA-seq with FusionPlex Myeloid kit (ArcherDX, CO, USA) followed by high-throughput sequencing identified novel fusion transcript KMT2A-BTK with exon 9-exon 2 breakpoint junction. Sanger sequencing was used for validation.…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Diagnosis and management of glutaric aciduria type I – revised recommendations
- EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
- Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
- Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.