t(11;14;19)(q23;q32;p13.1) with simultaneous KMT2A and IGH rearrangements

Adriana Zamecnikova  

Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait annaadria@yahoo.com

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-
Main items
-

Clinics case report

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

Blood data

Wbc
16.9
Hb
9.5
Platelets
112
Blasts
70%
Bone marrow
Hypercellular with 89% blasts.

Cyto path

Phenotype
(FAB) Acute myeloid leukemia (M4)
Immunophenotype
CD19 , CD79a , CD13,CD11b , CD 15, CD117, CD33, MPO, HLDR, CD34 and CD64 positive, TdT dim (11%).
Precise diagnosis
AML with 11q23/MLL abnormalities.

Survival data

Date diagnosis
01-2017
Treatment
Chemotherapy
Complete remission
+ No remission after 1 month, complete cytogenetic remission after 2 months.
Treatment relat death
-
Relapse
-
Status
L
Date last follow
04-2017
Survival
2+

Karyotype

Sample
Bone marrow
Culture time
24
Banding
G-banding
Results
46,XX,t(11;14;19)(q23;q32.3;p13.1)
Mol cytogenet technics
Fluorescence in situ hybridization (FISH) with LSI PML/RARA, LSI RUNX1/RUNX1T1, LSI CBFB(inv(16), LSI KMT2A (MLL) break apart, LSI IGH break-apart, LSI BCR-ABL1 (Abbott/Vysis, Downers Grove, IL, USA) and Kreatech KMT2A/MLLT1 probes (Leica Biosystems, US).
Mol cytogenet results
Applying KMT2A (MLL)/MLLT1 (ENL) revealed translocation of part of KMT2A sequences to der(14) chromosome and the signal for MLLT1 (ENL) located on 19p13.3 translocated to der(11) chromosome distal to KMT2A indicating t(11;19)((q23;p13.1).

Images

Atlas Image
Figure 1 (A)Karyotype and partial karyotypes of the patient showing the 3-way chromosome translocation t(11;14;19)(q23;q32;p13.1).
Atlas Image
Figure 2 (A) Fluorescence in situ hybridization FISH)with LSI KMT2A (MLL) break apart probe showing disruption of KMT2A and the presence of KMT2A Spectrum-Orange-labeled probe on der(14) chromosome indicative of translocation of 11q23 to der(14) chromosome. (B) FISH with LSI IGH break apart probe revealed translocation of IGH 5 variable region sequences (green signal)to der(19) chromosome indicative of translocation of 14q32 to chromosome 19. (C) FISH using KMT2A/MLLT1 probe showing translocation of telomeric part of KMT2A sequences to der(14) chromosome and the juxtaposition of MLLT1 located on 19p13.3 to der(11) chromosome distal to KMT2A indicative of t(11;19)((q23;p13.1). (D) Simultaneous hybridization with KMT2A and IGH break-apart probes showing a double sized red-red signal on der(14) as a result of juxtaposition of part of KMT2A sequences (red) to the disrupted IGH sequences (red) on der(14) chromosome.

Comments section

Comments
The KMT2A gene is frequently disrupted by various chromosomal rearrangements, comprising a distinct clinical entity despite a large variety of partner genes. On the other hand, chromosomal translocations involving IGH are associated mainly with mature B-cell neoplasms and they are infrequent in acute leukemia (Jaso et al., 2013). Simultaneous occurrence of these 2 anomalies either in the same or separate clones has been described only in sporadic cases (Jeffries et al., 2014). We described here a patient with a 3-way translocation t(11;14;19)(q23;q32;p13) and co-existence of the KMT2A and IGH rearrangements. The juxtaposition of 19p13.1 sequences to 11q23 suggest the presence of KMT2A-ELL rearrangement on der(11) chromosome. The translocation of the disrupted KMT2A sequences to rearranged IGH locus may indicate formation of IGH-KMT2A fusion on der(14) chromosome with simultaneous translocation of IGH sequences to 19p13.1. While we cannot confirm the sequence of events, the presence of t(11;19)(q23;p13.1) on der(11) suggest the emergence of this known primary anomaly prior to the IGH translocation.

Bibliography

Pubmed IDLast YearTitleAuthors
240307422014B acute lymphoblastic leukemia with t(14;19)(q32;p13.1) involving IGH/EPOR: a clinically aggressive subset of disease.Jaso JM et al
248162342014IGH@ translocations co-exist with other primary rearrangements in B-cell precursor acute lymphoblastic leukemia.Jeffries SJ et al

Citation

Adriana Zamecnikova

t(11;14;19)(q23;q32;p13.1) with simultaneous KMT2A and IGH rearrangements

Atlas Genet Cytogenet Oncol Haematol. 2019-12-01

Online version: http://atlasgeneticsoncology.org/case-report/208899/t(11;14;19)(q23;q32;p13-1)-with-simultaneous-kmt2a-and-igh-rearrangements