CASE REPORTS in HAEMATOLOGY (Paper co-edited with the European LeukemiaNet)

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

Written	2011-03	Adriana Zamecnikova
		Kuwait Cancer Control Center, Dep of Hematology, Laboratory of Cancer Genetics, Kuwait

Clinics

Age and sex :	3 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 : 3.2 x 109/L ; Hb : 9.8 g/dL ; platelets : 52 x 109/L; blasts : 29 % (Neutrohils 8 Lymphocytes 61% Eosinophils 2% atypical lymphocytes 29%).

Bone marrow : Hypercellular, with 70% lymphoblasts replacing normal marrow elements

Cyto pathology classification

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

Date of diagnosis: 01-2011

Karyotype

Sample : Bone marrow ; culture time : 24 h ; banding : G-band

Results : 48,XX,+16,+18

Other molecular cytogenetics technics : Fluorescence in situ hybridization with LSI TEL-AML1 (ETV6-RUNX1), LSI IGH/BCL2 and LSI CBFB probes

Other molecular cytogenetics 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 molecular studies

technics : RT-PCR for TEL-AML1

results : Positive

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

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.

Internal links

Atlas Card	+16 or trisomy 16 (solely)
Atlas Card	+18 or trisomy 18 in lymphoproliferative disorders

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Citation

This paper should be referenced as such :

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Reports/tri16tri18ZamecnikID100049.html

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