KMT2A Rearrangement Type

Based on the retrieved evidence, KMT2A rearrangements (KMT2A-r) involve the **KMT2A gene** (formerly *MLL*) located on chromosome 11q23.3. These are recurrent genetic abnormalities in acute leukemias, with over 130 different fusion partner genes identified [1][7]. The specific fusion partner is a critical determinant of clinical features, prognosis, and risk stratification. ### Common KMT2A Rearrangement Types and Their Clinical Significance The following table summarizes the most frequently reported KMT2A fusion partners, their associated translocations, and their prognostic implications based on the retrieved literature. | KMT2A Fusion Partner | Translocation | Frequency & Disease Context | Prognostic Risk Group (ELN 2022 / Pediatric Consensus) | | :--- | :--- | :--- | :--- | | **KMT2A::MLLT3** | t(9;11)(p22;q23) | Most common in adult AML (~33% of KMT2A-r AML) [1]. Also seen in B-ALL (~16%) [10]. | **Intermediate-risk** (ELN 2022) [1]. However, some studies suggest this favorable prognosis may be limited to younger patients (<60 years) [1]. | | **KMT2A::AFF1** | t(4;11)(q21;q23) | Most common in infant B-ALL (~50% of KMT2A-r B-ALL) [10]. Also seen in AML and mixed-phenotype acute leukemia (MPAL) [8]. | **Adverse-risk** [5][7]. Associated with poor prognosis, especially in infants [8]. | | **KMT2A::AFDN** | t(6;11)(q27;q23) | Common in adult AML (~23.6% in one cohort) [1]. | **Adverse-risk** [5][7]. Associated with hyperleukocytosis [1]. | | **KMT2A::MLLT1** | t(11;19)(q23;p13.3) | Common in AML and B-ALL (~20-22%) [1][10]. | **Adverse-risk** [5][7]. | | **KMT2A::MLLT10** | t(10;11)(p12;q23) | Seen in AML and B-ALL (~6-12%) [1][10]. | **Adverse-risk** [5][7]. | | **KMT2A::ELL** | t(11;19)(q23;p13.1) | Seen in AML [1]. | **Adverse-risk** (often grouped with other non-MLLT3 rearrangements) [1]. | | **KMT2A::ABI1** | t(10;11)(p11.2;q23) | Rare, seen in pediatric AML [5]. | **Adverse-risk** [5][7]. | | **KMT2A::MLLT11** | t(1;11)(q21;q23) | Rare, reported in pediatric AML [5]. | **Favorable** (in some pediatric studies, though not consistently confirmed) [5]. | ### Key Clinical and Prognostic Insights 1. **Prognostic Heterogeneity**: The prognosis of KMT2A-r leukemia is highly dependent on the specific fusion partner, not merely the presence of the rearrangement itself [1][5][7]. 2. **Risk Stratification**: - **ELN 2022 (Adult AML)**: Classifies **KMT2A::MLLT3** as **intermediate-risk**, while all other balanced 11q23/KMT2A rearrangements are categorized as **adverse-risk** [1]. - **Pediatric AML**: A consensus from the I-BFM Study Group identifies five fusions (KMT2A::AFF1, KMT2A::AFDN, KMT2A::MLLT10, KMT2A::ABI1, KMT2A::MLLT1) as an **adverse-risk** group [5][7]. 3. **Impact of Co-occurring Mutations**: The prognostic impact of KMT2A-r can be further modified by co-occurring mutations. For example, **KRAS mutations** are more frequent in KMT2A::AFDN (t(6;11)) and are associated with adverse outcomes, potentially explaining some of the prognostic differences between fusion partners [1][6]. 4. **Therapeutic Implications**: Patients with adverse-risk KMT2A-r are typically referred for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1), which has been shown to be an independent favorable prognostic factor [1][9]. ### Conclusion KMT2A rearrangements encompass a diverse group of genetic abnormalities. The specific fusion partner is the primary determinant of risk stratification, with **KMT2A::MLLT3** generally considered intermediate-risk and most other partners (e.g., **KMT2A::AFF1**, **KMT2A::AFDN**, **KMT2A::MLLT1**, **KMT2A::MLLT10**) classified as adverse-risk. --- *This information is synthesized from retrieved literature for clinical reference. Individual patient management should be guided by the most current guidelines and clinical judgment.*