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

Written2016-07Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France.
This article is an update of :
2010-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France.

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

Keywords chromosome 1; chromosome2; t(1;2)(p36;p21); PRDM16; THADA

(Note : for Links provided by Atlas : click)


ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1542

Clinics and Pathology

Disease 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 / cell stem 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 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).


Cytogenetics Morphological In two cases, the t(1;2) was the sole anomaly (Horiike et al., 1988; Storlazzi et al., 2008). In contrast, complex karyotype were present in the 4 other cases. inv(14)(q11q32) was present in the T-ALL case (Mathew et al., 2001); del(5q) was found in 3 cases (Roulston et al., 1998; Mauritzson et al., 2002; Duhoux et al., 2012), del(7q) in one case (Masuya et al., 2002) and a del(20q) in one case (Duhoux et al., 2012). Other remarkable anomalies were: t(14;21)(q22;q22) with RUNX1 involvement (Roulston et al., 1998), +8, +12, +13 appearing during course of the disease (Masuya et al., 2002); there was also, in the latter case, an unrelated clone with t(11;12)(p15;q13).

Genes involved and Proteins

Note 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 NamePRDM16 (PR domain containing 16)
Location 1p36.32
Dna / Rna 11 splice variants
Protein 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 NameTHADA (THADA, armadillo repeat containing)
Location 2p21
Dna / Rna 19 splice variants
Protein 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

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

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Prdm16 is a physiologic regulator of hematopoietic stem cells.
Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW.
Blood. 2011 May 12;117(19):5057-66. doi: 10.1182/blood-2010-08-300145. Epub 2011 Feb 22.
PMID 21343612
The Multifaceted Roles of PRDM16: Adipose Biology and Beyond.
Chi J, Cohen P.
Trends Endocrinol Metab. 2016 Jan;27(1):11-23. doi: 10.1016/j.tem.2015.11.005. Epub 2015 Dec 11. Review.
PMID 26688472
Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
Chuikov S, Levi BP, Smith ML, Morrison SJ.
Nat Cell Biol. 2010 Oct;12(10):999-1006. doi: 10.1038/ncb2101. Epub 2010 Sep 12.
PMID 20835244
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Duhoux FP, Ameye G, Montano-Almendras CP, Bahloula K, Mozziconacci MJ, Laibe S, Wlodarska I, Michaux L, Talmant P, Richebourg S, Lippert E, Speleman F, Herens C, Struski S, Raynaud S, Auger N, Nadal N, Rack K, Mugneret F, Tigaud I, Lafage M, Taviaux S, Roche-Lestienne C, Latinne D, Libouton JM, Demoulin JB, Poirel HA; Groupe Francophone de Cytogénétique Hématologique (GFCH); Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO).
Br J Haematol. 2012 Jan;156(1):76-88. doi: 10.1111/j.1365-2141.2011.08918.x. Epub 2011 Nov 3.
PMID 22050763
Chromosome abnormalities and karyotypic evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis.
Horiike S, Taniwaki M, Misawa S, Abe T.
Cancer. 1988 Sep 15;62(6):1129-38.
PMID 3409186
Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM.
Nature. 2009 Aug 27;460(7259):1154-8. Epub 2009 Jul 29.
PMID 19641492
Two independent clones in myelodysplastic syndrome following treatment of acute myeloid leukemia.
Masuya M, Katayama N, Inagaki K, Miwa H, Hoshino N, Miyashita H, Suzuki H, Araki H, Mitani H, Nishii K, Kageyama S, Minami N, Shiku H.
Int J Hematol. 2002 Feb;75(2):182-6.
PMID 11939266
Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia.
Mathew S, Rao PH, Dalton J, Downing JR, Raimondi SC.
Leukemia. 2001 Mar;15(3):468-72.
PMID 11237073
Pooled 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, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z, Bjork J, Stromberg U, Nilsson PG, Mitelman F, Hagmar L, Johansson B.
Leukemia. 2002 Dec;16(12):2366-78.
PMID 12454741
Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas.
Rippe V, Drieschner N, Meiboom M, Murua Escobar H, Bonk U, Belge G, Bullerdiek J.
Oncogene. 2003 Sep 4;22(38):6111-4.
PMID 12955091
CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.
Roulston D, Espinosa R 3rd, Nucifora G, Larson RA, Le Beau MM, Rowley JD.
Blood. 1998 Oct 15;92(8):2879-85.
PMID 9763573
Upregulation 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, Albano F, Guastadisegni MC, Impera L, Muhlematter D, Meyer-Monard S, Wuillemin W, Rocchi M, Jotterand M.
Blood Cells Mol Dis. 2008 May-Jun;40(3):452-5. Epub 2008 Feb 21.
PMID 18178491


This paper should be referenced as such :
Jean Loup Huret
t(1;2)(p36;p21) THADA/PRDM16
Atlas Genet Cytogenet Oncol Haematol. 2017;21(4):162-163.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. t(1;2)(p36;p21). Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):80-81.

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;2)(p36;p21) THADA/PRDM16

External links

Mitelman databaset(1;2)(p36;p21)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
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