Trisomy 16 and 18 in acute lymphoblastic leukemia patient with ETV6-RUNX1 rearrangement

Adriana Zamecnikova  

Kuwait Cancer Control Center, Dep of Hematology, Laboratory of Cancer Genetics, Kuwait

Previous history

Preleukaemia
-
Malignant disease
-
Inborn condition
-

Clinics case report

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

Blood data

Wbc
3.2
Hb
9.8
Platelets
52
Blasts
29 Neutrohils 8%, Lymphocytes 61%, Eosinophils 2%, atypical lymphocytes 29%
Bone marrow
Hypercellular, with 70% lymphoblasts replacing normal marrow elements

Cyto path

Cytology
ALL
Immunophenotype
Positive for CD10 (90%), CD19 (81%), CD22 (81 %), 13 (61%), 33 (82%), 79a (38%), 34 (82%), HLDR (90%) and TdT (56%)
Precise diagnosis
B-lineage ALL

Survival data

Date diagnosis
01-2011
Date last follow
01-2011

Karyotype

Sample
Bone marrow
Culture time
24h
Banding
G-band
Results
48,XX,+16,+18
Mol cytogenet technics
Fluorescence in situ hybridization with LSI TEL-AML1 (ETV6-RUNX1), LSI IGH/BCL2 and LSI CBFB probes
Mol cytogenet results
Applying the LSI TEL-AML1 probe on bone marrow cells we detected in 70% of cells fusion signal for TEL-AML1. Applying the LSI IGH/BCL2 and LSI CBFB probes on metaphases we detected 3 copies for BCL2 and CBFB confirming the presence of extra chromosomes 16 and 18.

Other molec studies

Technics
RT-PCR for TEL-AML1
Results
Positive

Images

Atlas Image
Karyotype of the patient showing the presence of extra chromosomes 16 and 18 (A). Fluorescence in situ hybridization studies with LSI IGH/BCL2 and CBFB probes showing the presence of 3 copies of BCL2 and CBFB probes on chromosomes 16 and 18 (B). Hybridization with LSI TEL-AML1 (ETV6-RUNX1) probe showing the fusion signals on interphase cells (C).

Comments section

Comments
Current evidence suggests that in childhood acute lymphoblastic leukemia (ALL) with t(12;21), while the translocation may initiate the leukemic process, secondary genetic events are believed to be pivotal in disease promotion. We report a case of a patient displaying trisomy 16 and 18 as the sole cytogenetic anomaly detected by karyotyping. The patient, a previously healthy 3 years old female presented with fever and pancytopenia. Immunophenotyping showed B-lineage ALL, with aberrant expression of myeloid markers. Chromosome analysis performed at diagnosis revealed extra copies of chromosomes 16 and 18 in all the 20 examined metaphases. Fluorescence in situ studies revealed ETV6-RUNX1 fusion signal in 70% of cells and the rearrangement was confirmed by reverse-transcriptase polymerase chain reaction. While extra copies of chromosomes 16 and 18 may be observed in pediatric ALL patients with hyperdiploid karyotypes suggesting that they may exists as an evolutionary change, isolated trisomy 16 or 18 have been reported only rarely. A case similar to ours was previously reported in a child cytogenetically characterized by an isolated trisomy 16 and ETV6-RUNX1 fusion. Our case together with the previously reported case of B-cell ALL with ETV6-RUNX1 rearrangement suggests that trisomy of chromosome 16 and is an important additional or secondary genetic event in childhood ALL with ETV6-RUNX1 fusion. In addition, several cases of pediatric ALL with isolated trisomy 16 or 18 were reported potentially harboring the ETV6-RUNX1 rearrangement. As the translocation t(12;21) usually escapes diagnosis on conventional karyotyping, our case further reinforces the importance of fluorescence in situ hybridization studies in pediatric leukemias to reveal cryptic genomic rearrangements in addition to visible cytogenetic changes.

Article Bibliography

Pubmed IDLast YearTitleAuthors

Citation

Adriana Zamecnikova

Trisomy 16 and 18 in acute lymphoblastic leukemia patient with ETV6-RUNX1 rearrangement

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

Online version: http://atlasgeneticsoncology.org/case-report/208847/case-report-explorer/meetings/js/lib/zoomerang.js