Test Directory

KMT2A (MLL), 11q23.3

Mixed-lineage leukemia (MLL) abnormalities are frequently found in infant leukemias and therapy-related leukemias. Acute myeloid leukemia (AML) with lysine methyltransferase 2A (KMT2A) rearrangement is a myeloid neoplasm in which the KMT2A locus on chromosome 11q23.3 is fused with any of several partner genes. KMT2A gene rearrangements result from deletions, duplications, inversions, and translocations at the 11q23 locus. More than 80 fusion partners have been described in KMT2A rearranged AML. Overall, MLLT3, AFDN, ELL, and MLLT10 are most commonly implicated in KMT2A-rearranged AML, resulting from the translocations t(9;11)(p22;q23), t(6;11)(q27;q23), t(11;19)(p13.1;q23), and t(10;11)(p12;q23), respectively. As compared to AML with normal karyotype, the presence of KMT2A rearrangement is associated with a lower mutation burden. Adult patients predominantly have mutations in genes encoding the reticular activating system (RAS) pathway (NRAS, KRAS and PTPN11). FLT3 tyrosine kinase domain mutations (TKD), as well as mutations in RUNX1, TET2, PLCG2 and ZRSR2, have also been described. Mutations in NRAS, KRAS, PTPN11 and FLT3-TKD often occur at low (<20%) variant allele fractions indicating a subclonal nature. Mutations in DNMT3A, NPM1, CEBPA and FLT3 internal tandem duplication are uncommon. FISH can detect this abnormality in either interphase or metaphase cells.

Specimen Types: Leukemic Blood or Bone Marrow

Preferred Collection Container: Green Top (Sodium Heparin)

Alternate Collection Container: Lavendar Top (EDTA)

Desired Specimen Volume: 3 - 5 mL

Minimum Acceptable Volume: 1 mL

• Lithium heparin is not acceptable.
• Specimens must be collected in a sterile collection container.

Each specimen must be accompanied by a requisition form, script, electronic order or physician note. Each order must indicate the reason for testing (diagnosis).

• Transport to the laboratory at room temperature.
• Store specimen as whole blood, in original tube, at room temperature and deliver to lab within 24 hours.
• If specimen cannot be delivered within 24 hours, store in refrigerator. Do not freeze specimen.
• Specimens collected on the weekends must be refrigerated upon arrival at HNL Lab Medicine.

• Specimen frozen
• Specimen arriving without any form of patient identification (unlabeled)
• Specimen with attached needles
• Specimen arriving with broken or leaking collection tube
• Unfixed specimen treated with fixative

In a normal cell, the expected signal pattern is two fusion signals. In an abnormal cell containing a rearrangement, the expected signal pattern is one red signal, one green signal, and one fusion signal.

• FISH MLL BA
• KMT2A BA
• KMT2A Breakapart
• MLL Breakapart
• KMT2A
• MLL
• Mixed-Lineage Leukemia