HAEM5:Myeloid/lymphoid neoplasms with other tyrosine kinase fusion genes

Haematolymphoid Tumours (WHO Classification, 5th ed.)

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Primary Author(s)*

Put your text here (Rolando Garcia, PhD)

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	Myeloid proliferations and neoplasms
Family	Myeloid/lymphoid neoplasms
Type	Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangement
Subtype(s)	Myeloid/lymphoid neoplasms with other tyrosine kinase fusion genes

Related Terminology

Acceptable	N/A
Not Recommended	Myeloid/lymphoid neoplasms with tyrosine kinase fusion genes (NOS)

Gene Rearrangements

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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
FGFR2	ETV6::FGFR2	Fusion between exon 4 of ETV6 and exon 5 of FGFR2 (5′ to 3′ orientation).	Cryptic rearrangement detected by FISH involving chromosomes 10 and 12	Rare < 5%	D, P, T	Yes (WHO)	Myeloid / lymphoid acute leukemia. This fusion suggests abnormal FGFR2 expression. Aberrant The FGFR2 activation resulting from ETV6::FGFR2 may respond to FGFR1,2,3 tyrosine kinase inhibitors (TKIs). This rearrangement exhibited aggressive clinical behavior, demonstrating resistance to both conventional and intensive chemotherapy, as well as allogeneic stem cell transplantation. The prognosis remains unclear due to the limited number of cases.
LYN	ETV6::LYN	Fusion between exon 5 in ETV6 to exon 8 in LYN (5′ to 3′ orientation to produce an in-frame chimeric fusion)	Complex rearrangements involving chromosomes 8 and 12 [e.g. t(8;12)(q12;p13), ins(12;8)(p13;q11q21)]	Rare < 5%	D. P,T	Yes (WHO)	Acute myeloid leukemia / primary myelofibrosis/ T-lymphoblastic leukemia. Resistant to intensive chemotherapy or stem cell transplant, the disease progressed rapidly to terminal AML. Prognosis is not well defined due to the small number of cases.
NTRK3	ETV6::NTRK3	Fusion between ETV6 and NTRK3 (5′ to 3′ orientation)	t(12;15)(p13;q25)	Rare < 5%	T	Yes (WHO)	ETV6::NTRK3 is reported in multiple cancers but rare in acute lymphoblastic leukemia. The ETV6::NTRK3 responded to the ALK inhibitory crizotinib. Prognosis is not well defined due to the small number of cases.
ALK	RANBP2::ALK	exon 18 of RANBP2 and exon 20 of ALK (5′ to 3′ orientation). Leads to constitutive autophosphorylation of ALK tyrosine kinase and activating downstream signaling.	inv(2)(p23q13) / t(2;2)(p23;q13)	Rare < 5%	D, P, T	Yes (WHO)	Acute myelomonocytic leukemia/ myeloproliferative leukemia. Resistant to intensive chemotherapy and allogeneic SCT. Poor clinical outcome. Prognosis is not well defined due to the small number of cases.
RET	BCR::RET	Fusion between BCR exon 4 with the RET exon 12 (5′ to 3′ orientation). Aberrant expression of the kinase domain.	t(10;22)(q11;q11)	Rare <5%	D, P, T	Yes (WHO)	Associated with chronic myelomonocytic leukemia and monocytic differentiation. Sensitive to Sorafenib, an inhibitor to tyrosine kinase activity. The prognosis not well defined due to the limited number of cases.
RET	FGFR1OP::RET	Fusion between FGFR1OP exon 12 with RET exon 12 (5′ to 3′ orientation). Abnormal expression of the tyrosine kinase domain.	t(6;10)(q27;q11)	Rare <5%	D, P, T	Yes (WHO)	Associated with chronic myelomonocytic leukemia and monocytic differentiation. The prognosis remains unclear due to the limited number of cases.

Individual Region Genomic Gain/Loss/LOH

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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
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7	EXAMPLE: Unknown	EXAMPLE: D, P	EXAMPLE: No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8	EXAMPLE: Unknown	EXAMPLE: D, P		EXAMPLE: Common recurrent secondary finding for t(8;21) (add references).
EXAMPLE: 17	EXAMPLE: Amp	EXAMPLE: 17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]	EXAMPLE: ERBB2	EXAMPLE: D, P, T		EXAMPLE: Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

Characteristic Chromosomal or Other Global Mutational Patterns

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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
EXAMPLE: Co-deletion of 1p and 18q	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).	EXAMPLE: Common (Oligodendroglioma)	EXAMPLE: D, P
EXAMPLE: Microsatellite instability - hypermutated		EXAMPLE: Common (Endometrial carcinoma)	EXAMPLE: P, T

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

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
EXAMPLE:EGFR	EXAMPLE: Exon 18-21 activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (lung cancer)	EXAMPLE: T	EXAMPLE: Yes (NCCN)	EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations	EXAMPLE: Variable LOF mutations	EXAMPLE: Tumor Supressor Gene	EXAMPLE: Common (breast cancer)	EXAMPLE: P		EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations	EXAMPLE: Activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (melanoma)	EXAMPLE: T

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

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Genes and Main Pathways Involved

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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

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Familial Forms

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Additional Information

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Links

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References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):

*Citation of this Page: “Myeloid/lymphoid neoplasms with other tyrosine kinase fusion genes”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/11/2025, https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasms_with_other_tyrosine_kinase_fusion_genes.