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.

Etiology

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.

Epidemiology

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.

Clinics

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).

Prognosis

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.

Cytogenetics

Additional anomalies

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

Result of the Chromosomal Anomaly

Description

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

Bibliography

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

Summary

Note

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

Citation

Jean-Loup Huret

11q23 rearrangements (KMT2A) in therapy related leukaemias

Atlas Genet Cytogenet Oncol Haematol. 1998-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1131/11q23secondleukid1131

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