t(1;2)(p36;p21) THADA/PRDM16

2016-07-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr


Review on t(1;2)(p36;p21) translocations, with data on clinics, and the genes involved.

Clinics and Pathology


A t(1;2)(p36;p21) was found in primary myelofibrosis, myelodysplastic syndrome (MDS) in most cases, and T-cell acute lymphoblastic leukemia (T-ALL).

Phenotype stem cell origin

At least 3 of the 8 available cases were treatment related myelodysplastic syndromes (t-MDS) (Roulston et al., 1998; Mauritzson et al., 2002; Masuya et al., 2002), and 2 other cases were MDS (Horiike et al., 1988; Storlazzi et al., 2008).


CLINICS A 38-year-old male patient presented with a treatment related myelodysplastic syndrome (t-MDS) evolving towards an acute myeloid leukemia (t-AML). Previous treatment included topoisomerase inhibitors for a Hodgkin disease 36 months before diagnosis of the t-MDS (Roulston et al., 1998). A t-MDS was diagnosed in a 76-year-old female patient previously treated with radiotherapy for uterine cancer 29 years ago. She died 26 months after diagnosis of the t-MDS (Mauritzson et al., 2002). A 49-year-old female patient was diagnosed with t-MDS (FAB refractory anemia (RA)); she had been treated with etoposide 2 years previously for M1-AML; the patient died 6.5 years after onset of the t(1;2). Other chromosome anomalies appeared during course of the disease, as well as an unrelated clone (Masuya et al., 2002). A 67-year-old female patient had a chronic myelomonocytic leukemia (CMML) with a normal karyotype; she received hydroxyurea. Three years later, a refractory anemia with excess of blasts-2 (RAEB-2) and a t(1;2) was diagnosed. The patient died one month later (Storlazzi et al., 2008). Refractory anemia with excess of blasts (RAEB) was diagnosed in a 69-year-old male patient. The patient was still alive 15 months after diagnosis (Horiike et al., 1988). A 63-year old male patient presented with myelofibrosis, and was lost to follow up (Duhoux et al., 2012). A T-cell acute lymphoblastic leukemia (T-ALL) was found in a 1-year-old child (Mathew et al., 2001), and another one in a 79-year old female patient, who died one month after diagnosis (Duhoux et al., 2012).

Genes Involved and Proteins

In only three cases (the myelofibrosis case, one MDS, and one T-ALL), the genes likely to be involved in the translocation were determined: PRDM16 and probably THADA (Storlazzi et al., 2008; Duhoux et al., 2012).
Gene name
PRDM16 (PR domain containing 16)
Dna rna description
11 splice variants
Protein description
1276 amino acids and smaller proteins. Contains a N-term PR domain; 7 Zinc fingers, a proline-rich domain, and 3 Zinc fingers in the C-term. Binds DNA. Transcription activator; PRDM16 has an intrinsic histone methyltransferase activity. PRDM16 forms a transcriptional complex with CEBPB. PRDM16 plays a downstream regulatory role in mediating TGFB signaling (Bjork et al., 2010). PRDM16 induces brown fat determination and differentiation. PRDM16 is expressed selectively in the earliest stem and progenitor hematopoietic cells, and is required for the maintenance of the hematopoietic stem cell pool during development. PRDM16 is also required for survival, cell-cycle regulation and self-renewal in neural stem cells (Chuikov et al., 2010; Kajimura et al., 2010; Aguilo et al., 2011; Chi and Cohen, 2016).
Gene name
THADA (THADA, armadillo repeat containing)
Dna rna description
19 splice variants
Protein description
1953 amino acids and smaller proteins. Contains a poly-lysine stretch, a coiled coil domain, a poly-leucine stretch and a poly-alanine stretch. A strong expression of THADA is seen in pancreas and testis. THADA was found to be a ligand of death receptor DR5 and may be involved in the death receptor pathway and apoptosis. THADA was found to be fused to other partner genes in thyroid adenoma (Rippe et al., 2003).

Result of the Chromosomal Anomaly


Overexpression of PRDM16, but no significant change in the expression of THADA (Storlazzi et al., 2008; Duhoux et al., 2012)


Pubmed IDLast YearTitleAuthors
213436122011Prdm16 is a physiologic regulator of hematopoietic stem cells.Aguilo F et al
266884722016The Multifaceted Roles of PRDM16: Adipose Biology and Beyond.Chi J et al
208352442010Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.Chuikov S et al
220507632012PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.Duhoux FP et al
34091861988Chromosome abnormalities and karyotypic evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis.Horiike S et al
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Kajimura S et al
119392662002Two independent clones in myelodysplastic syndrome following treatment of acute myeloid leukemia.Masuya M et al
112370732001Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia.Mathew S et al
124547412002Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001.Mauritzson N et al
129550912003Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas.Rippe V et al
97635731998CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.Roulston D et al
181784912008Upregulation of MEL1 and FLJ42875 genes by position effect resulting from a t(1;2)(p36;p21) occurring during evolution of chronic myelomonocytic leukemia.Storlazzi CT et al


Fusion gene



Jean-Loup Huret

t(1;2)(p36;p21) THADA/PRDM16

Atlas Genet Cytogenet Oncol Haematol. 2016-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1542/t(1;2)(p36;p21)

Historical Card

2010-04-01 t(1;2)(p36;p21) THADA/PRDM16 by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr