21q22 rearrangements (RUNX1) in treatment related leukemia

2003-10-01   Jean-Loup Huret 

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

Clinics and Pathology


Treatment related myelodysplasia (t-MDS) or acute non lymphocytic leukaemias (t-AML)


The study included 79 cases; t-MDS without progression to AML accounted for 15%, t-MDS progressing to AML for 18%, t-AML for the remaining 67%; there was no case of acute lymphoblastic leukaemia

Phenotype stem cell origin

MDS cases were frequently refractory anemia with excess of blasts cases; 58% of AML cases were M2 AML


Frequent antracyclin exposure


21q22 rearrangements were found in 15% of t-MDS/t-AML; 1M to 1F sex ratio


Age at diagnosis of the primary disease was 47 yrs (range 2-75); age at diagnosis of the t-MDS/t-AML was 51 yrs (11-77) and median interval was 39 mths (6-306). Primary disease was a solid tumor in 56% of cases (mainly: breast, lung, sarcoma/ PNET, colon cancer) and an hematologic malignancy in 43%. Treatment of the primary disease included radiotherapy (in 6%), chemotherapy (46%) or both (48%). 75% of patients with a 21q22 rearrangement had previously received topoisomerase II inhibitors, a higher proportion than other subgroups of treatment related leukemia, except 11q23 patients, who were 84% to have been exposed to topoisomerase II inhibitors; alkylating agents exposure was higher than in patients with t(15;17) or inv(16)


Patients who received bone marrow transplantation had a higher median survival (31 mths).


Median survival was 14 mths, there was 58% of patients surviving 1 yr, 33% 2 yrs, and 18% 5 yrs., a better outcome than patients with 11q23 rearrangement, 3q21q26 rearrangement, 12p13 rearrangement, t(9;22), or t(8;16) and a worse outcome than those with t(15;17) or inv(16) treatment related leukemias.By th 21q22 group, patients with a t(8;21) had a better outcome, and those with a t(3;21) had a worse outcome.


Cytogenetics morphological

t(8;21)(q22;q22) ( ETO / AML1) was found in 56% of cases, t(3;21)(q26;q22) ( MDS-EVI1 / AML1 in 20 %, t(16;21)(q24;q22) ( CBFA2T3 / AML1) in 5%. Rare recurrent anomalies were: t(1;21)(p36;q22), t(9;21)(p22;q22), t(10;21)(p12;q22), t(15;21)(q21-22;q22), t(17;21)(q12;q22), and t(20;21)(q11;q22)

Additional anomalies

-7/del(7q) in 23% of cases (espacially in cases with alkylating agents exposure), +8 in 11%, -5/del(5q) rarely found; complex karyotypes in 28% of cases (more frequently than in treatment related leukemias with a 11q23 rearrangement or a t(15.17))

Genes Involved and Proteins

Gene name
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))

Result of the Chromosomal Anomaly


5 AML1 - 3 partner


Pubmed IDLast YearTitleAuthors
11921272200221q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: report from an international workshop.Slovak ML et al



This data is extracted from a very large study from an International Workshop on treatment related leukemias - restricted to balanced chromosome aberrations (i.e.: -5/del(5q)and -7/del(7q) not taken into account per see), published in Genes, Chromosomes and Cancer in 2002.
Atlas Image
t(8;21)(q22;q22) RUNX1/RUNX1T1 . Fluorescence in situ hybridization with the Vysis LSI RUNX1/RUNX1T1 dual color dual fusion probes (Abbott Molecular, US) showing 2 copies of genes on normal (A) and fusion red-green signals on der(8) and der(21) chromosomes, the most frequently encountered FISH pattern in patients with t(8;21)(q22;q22) (B). Variations in the FISH patterns include the presence of 1 fusion signal on der(8) chromosome (C), insertion of RUNX1T1 into chromosome 21 (D) and cryptic fusion gene on der(21) with normal appearing chromosomes (E). Courtesy Adriana Zamecnikova.


Jean-Loup Huret

21q22 rearrangements (RUNX1) in treatment related leukemia

Atlas Genet Cytogenet Oncol Haematol. 2003-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1296/21q22-rearrangements-(runx1)-in-treatment-related-leukemia