t(1;22)(p13;q13) RBM15/MKL1
2001-06-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
Clinics and Pathology
Disease
only found so far in M7 AML (acute megakaryocytic leukaemia); not found in Down syndrome (DS), and yet, DS is a disease with highly elevated risk of M7 (see leukaemia and Down Syndrome); misdiagnoses of a solid tumour have been documented
Phenotype stem cell origin
megakaryocytic
Etiology
no known toxic exposure
Epidemiology
about 40 known cases; 0% to 3% of paediatric AML; 70 to 100% of infants M7; age: infants: median age 4 mths; 20% are < 1mth; 80% are < 1 yr; 95% are < 2 yrs; sex ratio: 15M/24F (non significant)
Clinics
no preceeding myelodysplasia, and no history of transient leukemoid reaction; prominent organomegaly; blood data: moderate WBC; thrombocytopenia; myelofibrosis and fibrosis of other organs
Cytology
platelet-specific markers: platelet-peroxidase by electron microscopy, or platelet glycoproteins IIb/IIIa (CD41) or IIIa (CD61)
Treatment
bone marrow transplantation is indicated
Prognosis
complete remission in only 50% of cases; median survival: 8 months; a few long survivors; absence of a prognostic indicator
Cytogenetics
Additional anomalies
60% of cases (mostly patients under 6 mths of age) have the t(1;22) as a single anomaly; the remaining third of cases (mainly patients above the age of 6 mths) exhibit complex and hyperploid clones, with a highly monomorph pattern: +2, +19, +der(1)t(1;22), +6, +21 were found in more than 50% of cases each, +10, +7, +15, +18, +8, +20, del(1p), +4, +9, +14, +17, add(21p) are also recurrent; survival was equivalent in cases with or without a complex karyotype; the frequent presence of an additional der(1) indicates that the crucial event is likely to lie on the der(1)t(1;22)
Variants
2 cases of complex t(1;22) with a third chromosome have been described
Genes Involved and Proteins
Gene name
RBM15 (RNA binding motif protein 15)
Location
1p13.3
Protein description
contains RNA recognition motif consensus
Gene name
MKL1 (megakaryoblastic leukemia (translocation) 1)
Location
22q13.1
Protein description
931 amino acids; could attach DNA to nuclear scaffold and be involved in chromatin organization
Result of the Chromosomal Anomaly
Description
5 OTT - 3 MAL, comprisng most of OTT fused to most of MAL; the reciprocal 5 MAL - 3 OTT may or may not be present
Oncogenesis
may modulate chromatin organization, HOX differentiation pathways, or extracellular signaling
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 32408494 | 2020 | RNA-Binding Proteins in Acute Leukemias. | 255 |
| 12944485 | 2003 | Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes. | 68 |
| 17283045 | 2007 | Rbm15 modulates Notch-induced transcriptional activation and affects myeloid differentiation. | 51 |
| 22927943 | 2012 | Rbm15-Mkl1 interacts with the Setd1b histone H3-Lys4 methyltransferase via a SPOC domain that is required for cytokine-independent proliferation. | 42 |
| 28112737 | 2017 | Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. | 41 |
| 27114462 | 2016 | Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study. | 39 |
| 26215111 | 2015 | Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. | 38 |
| 18710951 | 2008 | OTT-MAL is a deregulated activator of serum response factor-dependent gene expression. | 32 |
| 36003795 | 2022 | Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution. | 22 |
| 36798463 | 2023 | t(1;7;22)(p13;q21;q13) is a novel 3-way variant of t(1;22)(p13;q13) neonatal acute megakaryoblastic leukemia: A case report. | 18 |
| 25838902 | 2015 | Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma. | 15 |
| 28239626 | 2017 | Acute Myeloid Leukemia With RBM15-MKL1 Presenting as Severe Hepatic Failure. | 14 |
| 35844738 | 2022 | Case Report: The Value of Genomic Analysis in a Case of Megakaryoblastic Leukemia With Atypical Initial Manifestation. | 12 |
| 29806701 | 2018 | Neonatal leukaemia. | 0 |
| 28412998 | 2017 | New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia harboring the fusion oncogene RBM15-MKL1. | 0 |
| 15849773 | 2005 | RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient. | 0 |
| 34497221 | 2021 | [Acute leukemia of infants and neonates]. | 0 |
| 19860179 | 2009 | [Classification of myeloid leukemias]. | 0 |
| 22469944 | 2012 | Hemophagocytosis by leukemic megakaryoblasts in acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13;q13);RBM15-MKL1. | 0 |
| 32743872 | 2021 | TERT promotor variant associated with poor clinical outcome in a patient with novel RBM15-MKL1 fusion-positive pediatric acute megakaryoblastic leukemia. | 0 |
| 21370421 | 2011 | Acute megakaryoblastic leukemia with a four-way variant translocation originating the RBM15-MKL1 fusion gene. | 0 |
| 24743787 | 2014 | Detection of RBM15-MKL1 fusion was useful for diagnosis and monitoring of minimal residual disease in infant acute megakaryoblastic leukemia. | 0 |
| 30842387 | 2019 | [Prognostic significance of chimeric fusion gene analysis in pediatric acute megakaryoblastic leukemia]. | 0 |
| 32572949 | 2020 | Acute megakaryoblastic leukaemia with t(1;22)(p13·3;q13·1)/RBM15-MKL1 in an adult patient following a non-mediastinal germ cell tumour. | 0 |
| 28063190 | 2017 | Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome. | 0 |
| 31802626 | 2020 | Acute megakaryoblastic leukemia with t(1;22)(p13.3;q13.1); RBM15-MKL1 mimicking hepatoblastoma in an infant: The role of karyotype in differential diagnosis. | 0 |
| 29427526 | 2018 | NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy. | 0 |
| 23531517 | 2013 | NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. | 0 |
Bibliography
No bibliography items were found for this article.
Summary
Fusion gene
RBM15/MKL1 RBM15 (1p13.3) MKL1 (22q13.1) M|RBM15/MKL1 RBM15 (1p13.3) MKL1 (22q13.1) M t(1;22)(p13;q13)
t(1;22)(p13;q13) G- and R- banding
Citation
Jean-Loup Huret
t(1;22)(p13;q13) RBM15/MKL1
Atlas Genet Cytogenet Oncol Haematol. 2001-06-01
Online version: http://atlasgeneticsoncology.org/haematological/1005/deep-insight-explorer/
Historical Card
1999-11-01 t(1;22)(p13;q13) RBM15/MKL1 by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
1998-01-01 t(1;22)(p13;q13) RBM15/MKL1 by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
1997-08-01 t(1;22)(p13;q13) RBM15/MKL1 by Jean-Loup Huret,Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
