A new case of t(4;12)(q12;p13) in a secondary acute myeloid leukemia with review of literature

Sarah M Heaton, Frederick Koppitch, Anwar N Mohamed  

Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA

Previous history

Malignant disease
+ Hodgkin s Lymphoma, stage IVA at age 25 year, treated with ABVD for 12 months. Tumor mass in the upper cervical spine diagnosed at age 27 year, treated with laminectomy and five doses of radiation.
Inborn condition

Clinics case report

57 yrs
Lymph nodes
Cns involv

Blood data

Bone marrow
Variably cellular with 20% myeloblasts and dysplastic changes in the erythroid and myeloid cell lines.

Cyto path

His bone marrow showed 60% blasts, and dysplastic changes were noted in the erythroid and myeloid cell lines.
Flow cytometry (FCM) revealed that the blasts were of myeloid lineage expressing CD13, CD33, CD34, CD117, HLA-DR, and CD56.
Precise diagnosis
Acute myeloid leukemia (AML) with dysplastic changes.

Survival data

Date diagnosis
He was treated with Idarubicin+Ara-c (3+7) regimen. Because of 15% residual blasts in bone marrow, patient received additional 2+5 therapy, and then he underwent consolidation with Ara-C. Result of karyotype: 46,XY[20]. On April 2008, the patient received a matched unrelated female donor stem cell transplant (SCT). 30 days post transplant; bone marrow revealed no morphological evidence of leukemia and the karyotype was 46,XX[20]. On June 2008; patient developed pancytopenia; WBC: 2.2 x 109/l; Hb: 11.6 g/dl; platelets: 18.0 x 103/l. His bone marrow showed an increased dysplastic changes and <5% blasts, suggestive of possible early relapse. The karyotype became abnormal (see below). On June 2010; bone marrow was hypocellular with 20% blasts and dysplastic changes in the erythroid and myeloid lineages. FCM revealed myeloblasts expressing CD4, CD7, CD33, CD34, CD56, CD117 and HLA-DR. myeloperoxidase was negative. Non-specific esterase was positive in occasional blasts. Cytology: AML possibly of monocytic origin (AML-M5).
Complete remission
Treatment relat death
Phenotype relapse
Date last follow


Bone marrow
Culture time
24 and 48h with 10% conditioned medium
46,XY,t(4;12)(q12;p13)[6]/46,XX[14] in June 2008 (post transplant)
Karyotype relapse
46,XY,t(4;12)(q12;p13)[12]/ 46,idem,del(7)(q22q36)[4]/ 47,idem,+19[2]/ 46,XX[2], consistent with the recurrence and clonal evolution of the leukemic clone.
Mol cytogenet technics
Fluorescence in situ hybridization (FISH) using LSI 4q12 tricolor and LSI ETV6/RUNX1 ES dual color DNA probes were performed (Abbott Molecular. Downers Grove, IL) on the abnormal metaphase cells.
Mol cytogenet results
Translocation of the PDGFRA gene in Toto, spectrunAqua (SA), to derivative 12 and colocalized with centromeric region of ETV6; Break within ETV6 gene locus, sepctrunGreen (SG) and the telomeric region of ETV6 translocated to derivative 4 (Figure 2 A-C).


Atlas Image
Figure 1. G-banded karyotype showing the balanced t(4;12)(q12;p13) translocation.
Atlas Image
Figure 2. FISH on abnormal metaphases; (A) Metaphase hybridized with LSI 4q12 tricolor DNA probe showed a translocation of PDGFRA (SA) to derivative chromosome 12 (arrow), with the dual fusion of spectrunOrange (SO) and spectrunGreen (SG) remained on derivative 4. (B) Metaphase hybridized with LSI ETV6/RUNX1 ES dual color probe revealed a split of ETV6 (SG) with the smaller signal being translcated to derivative 4 (arrows). (C) Metaphase hybridized with both LSI 4q12 and ETV6/RUNX1 probes showed PDGFRA (SA) translocted to derivative 12 adjacent to ETV6 locus (arrows).

Comments section

The case reported here shared some features to those reported in the literature including positivity for CD7, CD33, CD34, CD117 and HLA-DR, lack of myeloperoxidase activity and dysplastic bone marrow. Unlike other reported cases, bone marrow basophilia and high platelets were not found. Clearly in our case, FISH showed a break within ETV6/12p13 gene, and colocalization of PDGFR1 gene to derivative 12 next to 5 ETV6 region.


Pubmed IDLast YearTitleAuthors
75454251995A specific chromosome abnormality of t(4;12)(q11-12;p13) in CD7+ acute leukaemia.Harada H et al
91306131997Characterization of acute leukemia with t(4;12).Harada H et al
94320541997CD7+ acute myeloid leukaemia with 'mature lymphoid' blast morphology, marrow basophilia and t(4;12)(q12;p13)Ma SK et al
94547711998Fluorescence in situ hybridization characterization of new translocations involving TEL (ETV6) in a wide spectrum of hematologic malignancies.Wlodarska I et al
104777091999Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).Cools J et al
105492631999A new translocation, t(2;4;12)(p21;q12;p13), in CD7-positive acute myeloid leukemia: a variant form of t(4;12).Hamaguchi H et al
125312292003t(4;12)(q11;p13): a rare chromosomal translocation in acute myeloid leukemia.Chauffaille Mde L et al
205135382010A rare t(4;12)(q12;p13) in an adolescent patient with acute myeloid leukemia.Manabe M et al


Sarah M Heaton, Frederick Koppitch, Anwar N Mohamed

A new case of t(4;12)(q12;p13) in a secondary acute myeloid leukemia with review of literature

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

Online version: http://atlasgeneticsoncology.org/case-report/208849/a-new-case-of-t(4;12)(q12;p13)-in-a-secondary-acute-myeloid-leukemia-with-review-of-literature