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(Paper co-edited with the European LeukemiaNet)
Second case of t(2;21)(q11.2;q22.3) in a child with T-cell acute lymphoblastic leukemia
Written2015-08Aurelia 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
Age and sex : 10 year(s) old female patient.
Previous History : no preleukemia (no pertinent past medical history)
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
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.
WBC : 29.8 x 109/L ; Hb : 13.4 g/dL ; platelets : 184 x 109/L; 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 pathology classification
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.
Date of 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 was obtained
Comments : Yes (still on therapy)
Treatment related death : -
Relapse : -
Status : Alive 08/2015
Survival : 3 month(s)
Sample : ; culture time : 24 h, 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 at relapse : N/A
Other molecular cytogenetics technics : text
Other molecular cytogenetics results : text
Other molecular 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
results : text
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).
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.
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.
Internal links
Atlas Cardt(2;21)(q11;q22)
Identification 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, Taki T, Nishida K, Shimizu D, Okuda T, Yoshida N, Kobayashi C, Koike K, Tsuchida M, Hayashi Y, Taniwaki M.
Oncogene. 2008 Apr 3;27(15):2249-56. Epub 2007 Oct 29.
PMID 17968322
Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).
Hiwatari M1, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y
Oncogene. 2003 May 8;22(18):2851-5.
PMID 12743608


This paper should be referenced as such :
Meloni-Ehrig A, Bohls N, Mahoney S, Curtis CA, Pare L, Johnston M, Aftab L, Hertzberg L
Second case of t(2;21)(q11.2;q22.3) in a child with T-cell acute lymphoblastic leukemia
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

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