| Clinics and Pathology |
| Disease | Acute promyelocytic leukaemia (M3-AML) |
| Note | In one case, a diagnosis of M1-AML was made, but there were some blasts suggestive of a microgranular variant of acute promyelocytic leukaemia (M3v-AML). |
| Epidemiology | 3 cases to date, 3 male patients aged 42, 57, and 67 years (Arnoud et al., 1999; Kusakabe et al., 2008; and Gallagher et al. (ref 6 in Kusakabe et al., 2008)). |
| Clinics | Patients exhibited normal WBC, mild anaemia, thrombocytemia and disseminated intravascular coagulation (DIC) (Kusakabe et al., 2008). |
| Treatment | One case did not respond to all trans-retinoic acid (ATRA) treatment, but ATRA revealed effective to control DIC, and was therefore continued. In another case, blasts failed to respond to ATRA in vitro. |
| Prognosis | Data is available in one case: the patient remains in complete remission 21 months after diagnosis. |
| Cytogenetics |
| Cytogenetics Morphological | Cryptic translocation. |
| Additional anomalies | -Y in two cases, i(17q) in one case. |
| Genes involved and Proteins |
| Gene Name | STAT5b |
| Location | 17q21 |
| Protein | Signal transduction (JAK/STAT signaling); Following JAK activation, STAT5B is phosphorylated, forms dimers and activates transcription. |
| Gene Name | RARA |
| Location | 17q21 |
| Protein | Ligand-dependent transcription factor specifically involved in hematopoietic cells differentiation and maturation. Receptor for all-trans retinoic acid (ATRA) and 9-cis RA. After linking with ATRA, RARA binds with RXR (retinoid X receptor protein) to the RARE domain (retinoic acid response elements), a DNA sequence common to a number of genes. |
| Result of the chromosomal anomaly |
| Description | 5' STAT5B - 3' RARA. Fusion of STAT5B (at exon "n") to exon 3 of RARA. The genes are normally separated by 1.9 Mb on chromosome 17q21; RARA transcription is centromere to telomere, while STAT5B is telomere to centromere. It was therefore presumed that the hybrid gene result from a small inversion (Kusakabe et al., 2008). |
| Description | Fusion protein of 1038 amino acids, composed of the NH2 term coiled-coil domain, the DNA binding domain the SH3 and the SH2 from STAT5B, fused to the transactivation domain, the DNA binding domain, the N-CoR box, and the COOH term ligand binding domain and dimerization domain of RARA. |
| External links |
| Other database | t(17;17)(q21;q21) | Mitelman database (CGAP - NCBI) | |
| Other database | t(17;17)(q21;q21) | CancerChromosomes (NCBI) |
| 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. |
| Bibliography |
| The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. |
| Arnould C, Philippe C, Bourdon V, Gr goire MJ, Berger R, Jonveaux P. |
| Hum Mol Genet. 1999 Sep;8(9):1741-9. |
| PMID 10441338 |
| Detection of the STAT5B-RARA fusion transcript in acute promyelocytic leukemia with the normal chromosome 17 on G-banding. |
| Kusakabe M, Suzukawa K, Nanmoku T, Obara N, Okoshi Y, Mukai HY, Hasegawa Y, Kojima H, Kawakami Y, Ninomiya H, Nagasawa T. |
| Eur J Haematol. 2008 May;80(5):444-7. Epub 2008 Jan 23. |
| PMID 18221386 |
| Contributor(s) |
| Written | 03-2009 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France |
| Citation |
| This paper should be referenced as such : |
| Huret JL . t(17;17)(q21;q21); dup(17)(q12q21). Atlas Genet Cytogenet Oncol Haematol. March 2009 . URL : http://AtlasGeneticsOncology.org/Anomalies/t1717q21q21ID1456.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Feb 6 15:46:29 CET 2010 |
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