Acute myeloid leukaemia with RBM15::MRTFA fusion

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Myeloid Leukemia (AML) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1.

Primary Author(s)*

Jennelle C. Hodge, PhD, FACMG

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Acute myeloid leukaemia
Type Acute myeloid leukaemia with defining genetic abnormalities
Subtype(s) Acute myeloid leukaemia with RBM15::MRTFA fusion

WHO Essential and Desirable Genetic Diagnostic Criteria

WHO Essential Criteria (Genetics)* Detection of RBM15::MRTFA fusion by FISH and/or RT-PCR or a similar molecular technique
WHO Desirable Criteria (Genetics)* Detection of t(1;22)(p13.3;q13.1) by karyotype analyssi
Other Classification N/A

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

(Instructions: The table will have the related terminology from the WHO autocompleted.)

Acceptable
Not Recommended

Gene Rearrangements

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
RBM15(OTT) / MKL1(MAL) The majority of both genes retained in the fusion 5’ DEK and 3’NUP214(CAN) with the pathogenic derivative being hte der(22). t(1;22)(p13.3;q13.1) Rare (AML) D Yes (WHO) This AML subtype is classified based on the presence of a t(1;22)(p13.3;q13.1), which results in fusion of RBM15(OTT) at 1p13.3 [hg38] and MKL1(MAL) at 22q13.1 [hg38] with variable breakpoints[1][2]. Although both reciprocal fusions are expressed, the RBM15-MKL1 fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins[1]. Typically the RBM15-MKL1 fusion presents as the sole abnormality[3].The t(1;22) occurs in <1% of all AML cases and 10-1% of pediatric acute megakaryoblastic leukemia cases (REFERENCE). It is most frequent in infants (<6 months old) and young children (<3 years old) with Down syndrome and has a female predominance. Rarely it occurs in adults (REFERENCES). Translocation-confirmed cases with <20% blasts on aspirate smears should be correlated with the biopsy to exclude an artificially low count due to marrow fibrosis, and then if the blasts remain low, followed closely to monitor for development of more definitive evidence for AML (such as the occurrence of extramedullary disease or myeloid sarcoma)[3]. This translocation was originally associated with poor prognosis but some studies demonstrate good response to intensive chemotherapy with long disease-free survival[3]. Two retrospective studies in 2015 and 2016 of non-Down syndrome pediatric AMKL patients found that the RBM15-MKL1 fusion was present in 12% and 13.7% of cases, was associated with significantly younger onset, and was considered to have a relative risk classification of intermediate or standard[4][5]. However, the majority of studies showed this to be a high-risk disease compared with pediatric AMKL without t(1;22). Careful supportive care is likely required to prevent early death related to intensive chemotherapy[6], especially considering the very young age of patients with this AML subtype; differences in such care may cause the lack of prognostic consistency[4].

Individual Region Genomic Gain/Loss/LOH

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A

Characteristic Chromosomal or Other Global Mutational Patterns

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A

Gene Mutations (SNV/INDEL)

COSMIC does not have specific information on mutations related to this subtype of AML.

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

Not applicable

Genes and Main Pathways Involved

The molecular mechanism is not completely understand, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways[3][1]. Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program

Genetic Diagnostic Testing Methods

Karyotype, FISH, RT-PCR

Familial Forms

Not applicable

Additional Information

Not applicable

Links

RBM15

MKL1

References

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  1. ↑ 1.0 1.1 1.2 Ma, Z.; et al. (2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics. 28 (3): 220–221. doi:10.1038/90054. ISSN 1061-4036. PMID 11431691.
  2. ↑ Arber, Daniel A.; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254.
  3. ↑ 3.0 3.1 3.2 3.3 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p139-140.
  4. ↑ 4.0 4.1 Inaba, Hiroto; et al. (2015). "Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study". Blood. 126 (13): 1575–1584. doi:10.1182/blood-2015-02-629204. ISSN 1528-0020. PMC 4582334. PMID 26215111.
  5. ↑ de Rooij, Jasmijn D. E.; et al. (2016). "Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study". Blood. 127 (26): 3424–3430. doi:10.1182/blood-2016-01-695551. ISSN 1528-0020. PMC 5161011. PMID 27114462.
  6. ↑ Creutzig, Ursula; et al. (2004). "Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 22 (21): 4384–4393. doi:10.1200/JCO.2004.01.191. ISSN 0732-183X. PMID 15514380.


Notes

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Prior Author(s):


*Citation of this Page: “Acute myeloid leukaemia with RBM15::MRTFA fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 05/10/2025, https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_RBM15::MRTFA_fusion.

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