11q23 rearrangements (KMT2A) in therapy related leukaemias

1998-08-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Phenotype stem cell origin

these treatment related myelodysplasia (t-MDS) or leukaemias (t-AL) exhibit variable phenotypes: CMML or RAEB±T in MDS cases, AML most often (M4 or M5a mainly, M1, M2, M5b at times, ALL (and biphenotypic leukaemias), often CD19+; t(4;11) cases are frequently ALL cases.


11q23 rearrangements in treatment related leukaemias were thought to be found mainly following a treatment with anti-topoisomerase II (epipodophyllotoxins) or with an intercalating topoisomerase II inhibitor (anthracyclins), as for some 21q22 rearrangements; actually, they may also be found after alkylating agents treatment and/or radiotherapy; the prior cancer is variable: breast cancer, non-Hodgkin lymphoma, Hodgkin disease, leukaemia, lung carcinoma, and other malignancies.


up to 30% of t(11;19)(q23;p13.1), 10% or more of t(9;11), 5% of t(4;11) and 5% of t(10;11) are found in secondary leukaemias: altogether 5 to 10% of 11q23 leukaemias are treatment related; these 11q23 second leukaemias are found at any age, from infancy to elder age.


latency for the outcome of the second leukaemia after the first cancer is often short (med 2 yrs), but highly variable, and may not depend on the type of treatment received; it is however most often shorter than in cases of second leukaemias associated with -5/del(5q) or with -7/del(7q).


is poor, as in other therapy related leukaemias; in a recent excellent studyc (n=40), only 80% of patients achieved remission, 3/4 relapsed within a year; median remission duration being 5 mths.


Additional anomalies

del(6q), -7/del(7q), del(17p)

Result of the Chromosomal Anomaly


5 MLL - 3 partnerN-term AT hook and DNA methyltransferase from MLL fused to (little or most of) the partner C-term part.


Pubmed IDLast YearTitleAuthors
75794621995Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia.Pedersen-Bjergaard J et al
95932901998Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities. EU Concerted Action 11q23 Workshop.Secker-Walker LM et al



11q23 rearrangements are also -and more often- found in de novo leukaemia


Jean-Loup Huret

11q23 rearrangements (KMT2A) in therapy related leukaemias

Atlas Genet Cytogenet Oncol Haematol. 1998-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1131/11q23-rearrangements-(kmt2a)-in-therapy-related-leukaemias