| ICD-Topo |
C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho |
9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged
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| ICD-Morpho |
9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged
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| ICD-Morpho |
9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
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| ICD-Morpho |
9920/3 Therapy-related myeloid neoplasms
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| Atlas_Id |
1457 |
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t(2;11)(q37;q23) by G-banding and FISH with dual-color, break-apart MLL probe; Cecília, Manuel R Teixeira (left); partial GTG-banded karyotype of t(2;11)(q37;23) and FISH analysis using probe LSI MLL DCBA demonstrating a 11q23 MLL rearrangement with a fusion signal on the normal chromosome 11, a split 5'MLL signal on der(11) and a 3'MLL signal on der(2); courtesy Arjan Buijs and Ellen van Binsbergen (right). |
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| Disease |
Rare type of acute myeloid leukemia (AML) and therapy-related AML. |
| Phenotype / cell stem origin |
No specific AML FAB sub-type (two cases M4, one M2, one M5a and one NOS). |
| Etiology | Either de novo or therapy-related (prior cancer is variable: breast cancer, non-Hodgkin lymphoma and LLA). |
| Epidemiology | Five cases known in the literature; four adults and one child, sex ratio 2M/3F; (age range 14.4-76). |
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| Prognosis | Two cases showed poor survival, 9 and 17 months respectively, one case achieved remission after stem cell transplantation. The prognosis may be likely to be comparable with that of other entities with 11q23/MLL involvement, and worse in therapy related leukemias. |
| Gene Name | KMT2A (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Dna / Rna | 37 exons, spanning over 100 kb. In a centromeric to telomeric direction; 13 and 15 kb; coding sequence: 11.9 kb. |
| Protein | 3969 amino acids; 431 KDa; contains from N-term to C-term 3 AT hooks homologous to high mobility group proteins HMGA1 and HMGA2, binding to the minor grove of DNA; 2 speckled nuclear localisation signals; 2 repression domains RD1 and RD2: RD1 or CXXC: cystein methyl transferase, binds CpG rich DNA, has a transcriptional repression activity; RD2 recruits histone desacetylases HDAC1 and HDAC2; 3 plant homeodomains (cystein rich zinc finger domains, with homodimerization properties), 1 bromodomain (may bind acetylated histones), and 1 plant homeodomain; these domains may be involved in protein-protein interaction; a FYRN and a FRYC domain; a transactivation domain which binds CBP ; may acetylates H3 and H4 in the HOX area; a SET domain: methyltransferase; methyltates H3, including histones in the HOX area for allowing chromatin to be open to transcription. MLL is cleaved by taspase 1 into 2 proteins before entering the nucleus: a p300/320 N-term protein called MLL-N, and a p180 C-term protein, called MLL-C. The FYRN and a FRYC domains of native MLL associate MLL-N and MLL-C in a stable complex; they form a multiprotein complex with transcription factor TFIID.
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| SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23). |
| Cerveira N, Correia C, Bizarro S, Pinto C, Lisboa S, Mariz JM, Marques M, Teixeira MR |
| Oncogene. 2006 ; 25 (45) : 6147-6152. |
| PMID 16682951 |
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| Translocation 2;11 and other significant chromosome changes in acute monoblastic leukemia (M5) with clonal evolution: sequential clinical and cytogenetic studies. |
| DeLozier-Blanchet CD, Cabrol C, Werner-Favre C, Beris P, Engel E |
| Cancer genetics and cytogenetics. 1985 ; 16 (2) : 95-102. |
| PMID 3855693 |
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| Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias. |
| Fischer K, Fröhling S, Scherer SW, McAllister Brown J, Scholl C, Stilgenbauer S, Tsui LC, Lichter P, Döhner H |
| Blood. 1997 ; 89 (6) : 2036-2041. |
| PMID 9058725 |
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| Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide. |
| Winick NJ, McKenna RW, Shuster JJ, Schneider NR, Borowitz MJ, Bowman WP, Jacaruso D, Kamen BA, Buchanan GR |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1993 ; 11 (2) : 209-217. |
| PMID 8426196 |
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| A new subtype of MLL-SEPT2 fusion transcript in therapy-related acute myeloid leukemia with t(2;11)(q37;q23): a case report and literature review. |
| van Binsbergen E, de Weerdt O, Buijs A |
| Cancer genetics and cytogenetics. 2007 ; 176 (1) : 72-75. |
| PMID 17574968 |
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