KMT2A-CBL Fusion Gene Resulting from del(11)(q23.3q23.3) Identified by Chromosome Microarray Analysis - second report in AML

S Temenuzhka Boneva and Elisabeth Nacheva  

HSL Analystics LLP OncoGenomics, London UK and UCL Cancer Institute, UK; temenuzhka.boneva@hslpathology.com

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-

Clinics case report

Age
18 yrs
Sex
F
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-

Blood data

Wbc
1.3 (neut 0.1x109/L);
Hb
7.4
Platelets
55
Note
The marrow smears showed heavily infiltrated with medium sized cells, which are round, have minimal lightly basophilic agranular cytoplasm and inconspicuous nucleoli, with partially clumped nuclear chromatin. Some of the nuclei appear cleaved or folded. A minority of the cells has very immature chromatin and/or prominent nucleoli, and are more classically blasts. There are no Auer rods in either population. Very minimal evidence of maturing granulopoiesis and erythropoiesis is seen. Granulopoesis appears to have normal granulation. Erythropoiesis appears normoblastic and not grossly dysplastic. Some of the mature neutrophils appear dysplastic with abnormal nuclear stranding. Megakaryocytes are not seen.

Cyto path

Phenotype
AML with recurrent cytogenetic translocations
Immunophenotype
CD45lo/ SSClo blasts account for 61.2% of total BM intact single cells. Positive for: CD34, CD33, CD15, CD38, CD56, HLADR. By intracellular staining, these cells were entirely cCD34+ and 45% were cMPO+. These cells were negative for: TdT, cCD3- and cCD79a-.
Rearranged ig tcr
Not performed
Pathology
Not performed
Electron microscopy
Not performed
Precise diagnosis
Common Acute Myeloid Leukaemia.

Survival data

Date diagnosis
05-2017
Treatment
according to FLAG-Ida chemotherapy protocol.
Complete remission
+ Complete remission was obtained on 06/2017
Treatment relat death
-
Relapse
-
Status
A
Date last follow
08-2019
Survival
26

Karyotype

Sample
Bone marrow
Culture time
24
Banding
GTG
Results
46,XX[20] - All 20 G-banded metaphase cells analysed showed a female karyotype with no apparent cytogenetic abnormalities.
Karyotype relapse

Mol cytogenet technics
3. The target myeloid gene panel TruSight on a MiSeq platform (Illumina, USA) was used to screen mutational hotspots of 54 cancer-related genes relevant in myeloid malignancy as before (Boneva et al., 2017). Gene variances were reported at allele frequencies (VAF) >10% and at minimum read depth of 300 as per manufacturers criteria. We used the Catalogue of Somatic Mutations In Cancer (COSMIC), dbSNP and 1000 genome (>2%) to classify gene variants as either drivers, variants of unknown significance and/or germline polymorphisms (SNPs). Genome addresses are given according to hg19 (GRCH37).
Mol cytogenet results
Variants: The only mutation identified in this sample is a missense variance of the RUNX1 gene (NP_001745.2:p.Gly372Ser at 36164761) which is reported SNV which is predicted to be tolerated (http://cancer.sanger.ac and http://www.ncbi.nlm.nih. gov/SNP) and therefore considered indicative for disease only in the presence of cell morphology and immunophenotyping evidence (Genovese et al., 2014; Cargo et al., 2015 and reviewed in Steensma, 2018).

Images

Atlas Image

Comments section

Comments
The presented case provides further support to the investigative power of CMA and a reminder for the existence of rare and possibly recurrent 5 KMT2A -3 CBL fusion gene in adult AML.

Bibliography

Pubmed IDLast YearTitleAuthors
263925962015Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression.Cargo CA et al
292793772018Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.Chen B et al
126960712003Identification of CBL, a proto-oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia.Fu JF et al
254268382014Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence.Genovese G et al
287017302018The MLL recombinome of acute leukemias in 2017.Meyer C et al
235215012013Does BCR/ABL1 positive acute myeloid leukaemia exist?Nacheva EP et al
304827702018Clinical consequences of clonal hematopoiesis of indeterminate potential.Steensma DP et al

Citation

S Temenuzhka Boneva and Elisabeth Nacheva

KMT2A-CBL Fusion Gene Resulting from del(11)(q23.3q23.3) Identified by Chromosome Microarray Analysis - second report in AML

Atlas Genet Cytogenet Oncol Haematol. 2019-08-01

Online version: http://atlasgeneticsoncology.org/case-report/208896/kmt2a-cbl-fusion-gene-resulting-from-del(11)(q23-3q23-3)-identified-by-chromosome-microarray-analysis-second-report-in-aml