Table of Contents
Definition / general | Clinical features | Case reports | Microscopic (histologic) description | Positive stains | Negative stains | Molecular / cytogenetics descriptionCite this page: Mihova D. AML with t(9;11)(p22;q23); KMT2A::MLLT3 . PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaaml11q23.html. Accessed April 18th, 2024.
Definition / general
- MLL gene at 11q23 (HRX) encodes a DNA binding protein that positively regulates expression of target genes, including multiple HOX genes, by methylation of histone H3 lys4 / chromatin remodeling (OMIM: Lysine Specific Methyltransferase 2A; KMT2A [Accessed 9 February 2022], Atlas of Genetics and Cytogenetics [Accessed 9 February 2022])
- 9p22 is MLLT3 / AF9 gene
- Included in WHO 2008 as AML with recurrent cytogenetics
- 3 - 5% of AML (Anticancer Res 2005;25(3B):1931)
- 9 - 12% of childhood AML; 2% of adult AML
- Overlaps other categories, including high percentage of topo II inhibitor, therapy related AML; also ALL and biphenotypic leukemia (Blood 2003;102:2395)
Clinical features
- Symptoms: DIC, extramedullary myeloid sarcoma and tissue infiltration (gingiva, skin)
- Translocations occur in AML (intermediate prognosis) and ALL (poor prognosis) (Blood Cells Mol Dis 2008;40:192)
- Prognosis may be superior to other AML with 11q23 translocations
- MLL partial tandem duplication AML: prognosis varies from poor to similar to other AML (Br J Haematol 2006;135:438, Blood 2007;109:5164)
- Also present in 93% of normal cord blood samples at low levels (Leuk Res 2006;30:1091)
- Associated with normal karyotype or trisomy 11
Case reports
- 60 year old woman with therapy related ALL with MLL gene rearrangement following treatment of breast cancer (Korean J Lab Med 2010;30:255)
- MLL insertion with MLL-MLLT3 gene fusion in acute leukemia (Cancer Genet Cytogenet 2008;183:53)
Microscopic (histologic) description
- 20%+ blasts / blast equivalents (monoblasts / monocytes) in peripheral blood or bone marrow, usually myelomonocytic or monocytic (AML M4, M5) and occasionally AML with (M2) or without (M1) maturation
- Monoblasts are large cells with abundant, moderate to intensively basophilic cytoplasm, pseudopods, azurophilic granules, vacuoles; round nuclei, lacy chromatin and one or more prominent nucleoli
- Promonocytes have basophilic cytoplasm with granules and occasional large azurophilic granules, vacuoles; irregular and delicately convoluted nuclei
Positive stains
Negative stains
- Myeloperoxidase
- Children: CD34 and CD117 negative
- Adults: variable CD14, often negative / dim
Molecular / cytogenetics description
- Involves MLL mixed lineage or myeloid / lymphoid leukemia gene, present in both AML and ALL; also called HTRX1, HRX and ALL1
- FISH is more sensitive than conventional cytogenetics in detecting MLL; may also detect 11q22-25 rearrangements that are MLL negative (Am J Clin Pathol 2004;122:298)
Variant MLL translocations in AML: - > 80 translocations described, most commonly MLLT2(AF4) causing ALL; and MLLT3(AF9) causing AML
- Mixed phenotype acute leukemia has t(v;11q23)
- AML-MRC if t(2;11)(p21;q23) or t(11;16)(q23;p13.3)
- Diagnose as t-AML if history of cytotoxic therapy
- Other common translocations: 6q27 (MLLT4), 10p12 (MLLT10), 19p13.1 (ELL) and 19p13.3 (MLLT1)
