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CASE REPORTS in HAEMATOLOGY
(Paper co-edited with the European LeukemiaNet)
t(11;14;19)(q23;q32;p13.1) with simultaneous KMT2A and IGH rearrangements
 
Written2019-12Adriana Zamecnikova
Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait annaadria@yahoo.com
Clinics
Age and sex : 23 year(s) old female patient.
Previous History : no preleukemia
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
Blood
WBC : 16.9 x 109/L ; Hb : 9.5 g/dL ; platelets : 112 x 109/L; blasts : 70% % .
Bone marrow : Hypercellular with 89% blasts.
Cyto pathology classification
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
Date of diagnosis: 01-2017
Treatment : Chemotherapy
Complete remission was obtained
Comments : No remission after 1 month, complete cytogenetic remission after 2 months.
Treatment related death : -
Relapse : -
Status : L 04-2017
Survival : 2 month(s)
Karyotype
Sample : Bone marrow ; culture time : 24 h ; banding : G-banding
Results : 46,XX,t(11;14;19)(q23;q32.3;p13.1)
Other molecular cytogenetics 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).
Other molecular cytogenetics results : Normal FISH results for LSI PML/RARA, LSI RUNX1/RUNX1T1, LSI CBFB(inv(16) and LSI BCR/ABL1.
Interphase FISH revealed rearrangements of KMT2A (90%) and IGH (90%) genes. Applying the LSI KMT2A break apart probe on 10 metaphases revealed translocation of telomeric gene sequences (red signal) to der(14) chromosome indicative of translocation of 11q to chromosome 14.
Applying the LSI IGH break apart probe on 10 metaphases revealed translocation of telomeric gene sequences (green signal, IGH 5' variable region) to der(19) chromosome indicative of translocation of 14q32 to chromosome 19.
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).
Figure 1 (A)Karyotype and partial karyotypes of the patient showing the 3-way chromosome translocation t(11;14;19)(q23;q32;p13.1).
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
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
B acute lymphoblastic leukemia with t(14;19)(q32;p13.1) involving IGH/EPOR: a clinically aggressive subset of disease.
Jaso JM, Yin CC, Lu VW, Zhao M1, Abruzzo LV, You MJ, Yang Y, Luthra R, Medeiros LJ, Lu G.
Mod Pathol 2014 Mar;27(3):382-9.
PMID 24030742
 
IGH@ translocations co-exist with other primary rearrangements in B-cell precursor acute lymphoblastic leukemia.
Jeffries SJ, Jones L, Harrison CJ, Russell LJ.
Haematologica 2014 Aug;99(8):1334-42.
PMID 24816234
 

Citation

This paper should be referenced as such :
A. Zamecnikova
t(11;14;19)(q23;q32;p13.1) with simultaneous KMT2A and IGH rearrangements
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Reports/t111419KMT2AandIGHAdrianaID100101.html

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indexed on : Wed Jul 28 18:15:59 CEST 2021


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