The Translocation t(8;16)(p11;p13) Defines an AML Subtype with Distinct Cytology and Clinical Features

Hanslip, J; Swansbury, G. J.; Pinkerton, Ross; Catovsky, Daniel

doi:10.3109/10428199209053586

Cited by 40 publications

(27 citation statements)

References 36 publications

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“…5 Of the two leukemia-associated translocations, the t(8;16) is the more common, with an occurrence of four per 1000 AML patients. 11 Since the first report of the translocation t(8;16) over a decade ago, 12 numerous studies (reviewed by Velloso et al 13 ) have ascertained that this translocation is a recurring cytog-enetic abnormality mainly associated with acute myelogenous leukemia (AML) M4/M5 French-American-British (FAB) subtypes. 14 All 42 previously reported patients 6,13,15 share a similar clinicopathologic profile.…”

Section: Introductionmentioning

confidence: 99%

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

et al. 1997

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The CREB-binding protein (CBP) is a large nuclear protein that regulates many signal transduction pathways and is involved in chromatin-mediated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.3 and the MOZ gene on chromosome band 8p11. Although a fusion of these two genes as a result of the translocation is expected, attempts at detecting the fusion transcript by reverse transcriptase polymerase chain reaction (RT-PCR) have proven difficult; to date, only one inframe CBP/MOZ fusion transcript has been reported. We therefore sought other reliable means of detecting CBP rearrangements. We applied fluorescence in situ hybridization (FISH) and Southern blot analyses to a series of AML patients with a t(8;16) and detected DNA rearrangements of both the CBP and the MOZ loci in all cases tested. All six cases examined for CBP rearrangements have breakpoints within a 13 kb breakpoint cluster region at the 5′ end of the CBP gene. Additionally, we used a MOZ cDNA probe to construct a surrounding cosmid contig and detect DNA rearrangements in three t(8;16) cases, all of which display rearrangements within a 6 kb genomic fragment of the MOZ gene. We have thus developed a series of cosmid probes that consistently detect the disruption of the CBP gene in t(8;16) patients. These clones could potentially be used to screen other cancer-associated or congenital translocations involving chromosome band 16p13.3 as well.

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Section: Introductionmentioning

confidence: 99%

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

et al. 1997

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“…17,18,27 The series was supplemented with cases previously reported in the literature. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][21][22][23][25][26][27][28] Where possible, we contacted the authors to provide missing data and material. Archive cases from the literature were only included when a well-documented cytogenetic report and clinical data were available.…”

Section: Patientsmentioning

confidence: 99%

Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

Coenen

Zwaan

Reinhardt³

et al. 2013

Blood

116

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Key Points• Pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features.• Spontaneous remissions occur in a subset of neonatal t(8;16)(p11;p13) AML cases.In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n 5 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P 5 .14). Gene expression profiles of t(8;16) (p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. (Blood. 2013;122(15):2704-2713

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“…The t(8;16)(p11;p13) translocation is a well-described entity in both de novo and treatment-related AML (Hanslip et al, 1992). It involves a fusion between the CREB-binding protein (CBP) and the MOZ gene, a chromatin associated acetyltransferase.…”

Section: Case Reportmentioning

confidence: 99%

Spontaneous regression of congenital leukaemia with an 8;16 translocation

et al. 2000

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Summary. Congenital leukaemia (CL) is a rare disorder that presents with extramedullary infiltrates and a myeloid phenotype. CL can progress rapidly without adequate treatment, but, paradoxically, may also remit spontaneously. Because of the significant toxicity involved in delivering chemotherapy to newborns, it is important to identify those newborns who may not require treatment. We describe an infant who presented at 1 week of age with congenital myeloid leukaemia. Cytogenetic analysis revealed a t(8;16)(q11;p13) translocation. The infant's leukaemia underwent a spontaneous regression. This case further confirms the possibility of spontaneous remission in congenital leukaemia. Moreover, it suggests that the presence of a clonal cytogenetic aberration does not preclude the possibility of a spontaneous regression in CL.Keywords: congenital leukaemia, treatment, chemotherapy, transient leukaemia, t(8;16).Congenital leukaemia (CL) is defined as the appearance of a leukaemic process in the newborn and immediate neonatal period (Weitzman & Grant, 1997). CL is extremely rare and its biology and natural history are poorly understood. The need for, and type of, treatment required in these patients has not been established. There have been several reports of spontaneous remissions in CL (Sainati et al, 1996;Lampkin, 1997), as well as reports of successful treatment of infants with CL using chemotherapy. As anti-leukaemic therapy in infants carries a significant risk for morbidity and mortality, it is important to base treatment decisions in these infants on well-defined criteria. We report a case of congenital leukaemia with a t(8;16) translocation that underwent a spontaneous remission. The implications of this finding and the therapeutic dilemmas raised by this disorder are discussed. CASE REPORTThe patient was the product of a normal full-term pregnancy. At the age of 7 d, partially elevated, purple± blue cutaneous nodules were noted over most of the skin surface. A biopsy of a lesion revealed an infiltration of the dermis by immature haematopoietic cells. Immunohistochemical stains were positive for myeloperoxidase, CD68 and LCA (leucocyte common antigen) and negative for CD1a, s100, CD34, keratin and an (unspecified) pan B marker.On admission, physical examination revealed a well appearing female infant with multiple, partially elevated purplish skin lesions. There was no hepatosplenomegaly or lymphadenopathy.The haemoglobin level was 9´2 g/dl, platelets were 356 Â 10 9 /l. The leucocyte count was 10´7 Â 10 9 /l, with 80% lymphocytes, 13% neutrophils, 3% band forms, 2% monocytes and 2% blasts. A bone marrow aspirate revealed a hypercellular marrow that contained 70±80% myelomonoblasts consistent with an M4 subtype. Immunophenotyping of the bone marrow showed the cells to be positive for HLA-DR, CD11b, CD13, CD 14, CD33, CD 42, CD10 and CD19, and negative for CD34, CD20 and CD2. Cytogenetic studies of the bone marrow revealed an abnormal female karyotype of 46,XX, t(8;16)(q11;p13) in six out of 21 metaphases analy...

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The Translocation t(8;16)(p11;p13) Defines an AML Subtype with Distinct Cytology and Clinical Features

Cited by 40 publications

References 36 publications

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

Spontaneous regression of congenital leukaemia with an 8;16 translocation

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