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Leukemia - Acute

Recurrent genetic abnormalities

Acute myeloid leukemia with t(9;11)(p22;q23); MLLT3-MLL

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 7 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.


● 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 159555, Atlas of Genetics and Cytogenetics)
● 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 (Blood 2003;102:2395); also ALL and biphenotypic leukemia

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 (Br J Haematol 2006;135:438) to similar to other AML (Blood 2007;109:5164); of note, 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)

Micro 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

● Nonspecific esterase
● CD4 weak, CD33 bright, CD36 / CD64 coexpression, CD45, CD56 and HLA-DR

Negative stains

● Myeloperoxidase
● Children: CD34 and CD117 negative
● Adults: variable CD14, often negative / dim

Molecular description

● Involves MLL-mixed lineage or myeloid / lymphoid leukemia gene, present in both AML and ALL; is 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)

Molecular images

Partner genes     Diagram of MLL/ALL1 duplication

End of Leukemia - Acute > Recurrent genetic abnormalities > Acute myeloid leukemia with t(9;11)(p22;q23); MLLT3-MLL

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