Second case of t(2;21)(q11.2;q22.3) in a child with T-cell acute lymphoblastic leukemia

Aurelia Meloni-Ehrig, Nathan Bohls, Sean Mahoney, Christine A. Curtis, Lorraine Pare, Martin Johnston, Lalarukh Aftab, Lawrence Hertzberg  

Department of Cytogenetics, CSI Laboratories, 2580 Westside Parkway, Alpharetta, GA, USA (AME, NB, SM, CAC); Departments of Hematopathology, Flow Cytometry, CSI Laboratories, 2580 Westside Parkway, Alpharetta, GA, USA (LA, LH); Department of Hematology/Oncology, The Children s Hospital at Memorial University Medical Center, 4700 Waters Ave., Savannah, GA, USA(LP, MJ) / e-MAIL ameloni@csilaboratories.com

Previous history

Preleukaemia
- no pertinent past medical history
Malignant disease
-
Inborn condition
-
Main items
-

Clinics case report

Age
10 yrs
Sex
F
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-
Note
Patient presented with abdominal pain and tachycardia. chest x-ray unexpectedly revealed a mediastinal mass. Biopsy of this mass confirmed T-cell lymphoblastic 'lymphoma' but screening marrow aspiration revealed involvement with sufficient blasts for diagnosis of acute leukemia.

Blood data

Wbc
29.8
Hb
13.4
Platelets
184
Blasts
0% none seen in peripheral blood.
Bone marrow
70%. The bone marrow shows partial involvement of the marrow by blasts with abnormal T-cell phenotype similar to the patient s mediastinal mass. The blasts represent 72% of cells by flow cytometry. Reduced trilineage hematopoiesis is present in the background. No dysplasia is identified. Megakaryocytes are present in normal numbers and show normal morphology. Monocytes are not increased. Plasma cells are not increased. No iron is identified on Prussian blue stain. Differential: Blasts: 70%; Promyelocytes: 4%; Myelocytes: 2%; Metamyelocytes: 2%; Neutrophils: 5%; Eosinophils: 1%; Monocytes: 1%; Erythroblasts: 15%

Cyto path

Phenotype
L1 ALL
Immunophenotype
Flow cytometric analysis of the mediastinal mass shows mostly a T-lineage immature cell population (99% of analyzed events) expressing: cytoplasmic CD3, CD5, CD7, small subset CD11c, CD38, CD45, CD71 and TdT. Significantly negative for CD2, surface CD3, CD4, CD8, CD10, CD19, CD20, CD13/CD33 and CD34. Based on light scatter characteristics the cells are enlarged to medium in size and have no increase in side scatter.
Rearranged ig tcr
Unknown.
Precise diagnosis
T-cell lymphoblastic acute leukemia.

Survival data

Date diagnosis
04/2015
Treatment
Chemotherapy per children oncology group (cog) protocol aall1231: induction with vincristine, daunorubicin, prednisone, peg-asparaginase; intrathecal cytarabine/methotrexate. Flow cytometric remission after four weeks. Consolidation therapy with cyclophosphamide, cytarabine, vincristine, peg-asparaginase; intrathecal methotrexate. More therapy to follow.
Complete remission
+ Yes (still on therapy)
Treatment relat death
-
Relapse
-
Status
A
Date last follow
08/2015
Survival
3

Karyotype

Culture time
24 and 48 hours unstimulated
Banding
GTW t
Results
46,XX,t(2;21)(q11.2;q22.3),ins(3;?)(q21;?),del(5)(q15q31),del(6)(q13q21) [cp21]
Karyotype relapse
N/A
Mol cytogenet technics
text
Mol cytogenet results
text

Other molec studies

Technics
FISH ETV6-RUNX1 (12;21) dual-color ES translocation probe. Abbott Molecular, Des Planes, IL, USA.
Results
nuc ish(ETV6x2,RUNX1x3)[98/100].

Other findings

Note
text

Images

Atlas Image
GTW-banded abnormal karyogram showing the t(2;21)(q11.2;q22.3) and other rearrangements: 46,XX,t(2;21)(q11.2;q22.3),ins(3;?)(q21;?),del(5)(q15q31),del(6)(q13q21).
Atlas Image
Interphase FISH showing the splitting of one of the RUNX1 signals due to the t(2;21). ETV6 (12p13) is labeled in SpectrumGreen and RUNX1 (21q22) in SpectrumOrange. Arrows point to the split RUNX1.

Comments section

Comments
This is the second case of T-ALL with t(2;21)(q11.2;q22.3) and involvement of RUNX1. The first case, which was reported in 2008, affected a 6-year-old boy (Chinen et al. 2008). In the previous report, the authors demonstrated that the t(2;21) resulted in a fusion between the AFF3 (aka., LAF4) and the RUNX1 (aka., AML1) genes located at 2q11.2 and 21q22.3, respectively. In the present case, we used FISH to demonstrate the involvement of RUNX1 in the t(2;21). It is, therefore, reasonable to assume that the t(2;21) observed here leads to an AFF3-RUNX1 fusion as well. AFF3 belongs to a family of putative transcription factors also comprising AFF1 (4q21), AFF2 (Xq28), and AFF4 (5q31). In both previous and present cases, the t(2;21) is present together with other chromosome abnormalities. Both patients responded well to the therapeutic approach. According to Chinen and coauthors, their patient was treated on the Tokyo Children s Cancer Study Group (TCCSG) L04-16 extremely high-risk (HEX) protocol, including stem cell transplantation. He achieved complete remission after the induction phase. After the early consolidation phase and two courses of the consolidation phase, he received allogeneic bone marrow transplantation from an unrelated HLA-matched donor 4 months after diagnosis. At the time of the case report in 2008, he was in complete remission for 17 months. Our patient also responded favorably to the therapeutic protocol (induction with vincristine, daunorubicin, prednisone, peg-asparaginase; intrathecal cytarabine/methotrexate; flow cytometric remission after four weeks; consolidation therapy with cyclophosphamide, cytarabine, vincristine, peg-asparaginase; intrathecal methotrexate). She is in complete remission for 5 months. The present case report provides further support that the t(2;21) is a rare but recurrent finding in pediatric T-ALL. This translocation seems to occur together with other chromosome abnormalities. Patients have responded favorably to the therapy and have achieved complete remission.

Bibliography

Pubmed IDLast YearTitleAuthors
179683222008Identification of the novel AML1 fusion partner gene, LAF4, a fusion partner of MLL, in childhood T-cell acute lymphoblastic leukemia with t(2;21)(q11;q22) by bubble PCR method for cDNA.Chinen Y et al
127436082003Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).Hiwatari M et al

Citation

Aurelia Meloni-Ehrig, Nathan Bohls, Sean Mahoney, Christine A. Curtis, Lorraine Pare, Martin Johnston, Lalarukh Aftab, Lawrence Hertzberg

Second case of t(2;21)(q11.2;q22.3) in a child with T-cell acute lymphoblastic leukemia

Atlas Genet Cytogenet Oncol Haematol. 2015-08-01

Online version: http://atlasgeneticsoncology.org/case-report/208877/second-case-of-t(2;21)(q11-2;q22-3)-in-a-child-with-t-cell-acute-lymphoblastic-leukemia