Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9.
The t(9;22)(q34;q11) translocation occurs in chronic myeloid leukemia (CML) and adult B-cell acute lymphoblastic leukemia (ALL), leading to fusion of BCR to ABL1 and constitutive activation of ABL1 tyrosine kinase activity. The main BCR-ABL1 breakpoints result in P190 BCR-ABL1 or P210 BCR-ABL1 fusion proteins. The latter is found in almost all cases of CML and in one third of the cases of t(9;22)-positive adult B-ALL. P190 BCR-ABL1 is found in the remaining two thirds of t(9;22)-positive adult B-ALL cases but only exceptionally in CML. We describe here the first case of t(9;22)(q34;q11) associated with t(10;11)(p13;q14) in acute monocytic leukemia. The recurrent t(10;11)(p13;q14) translocation, usually found in acute myeloid leukemia (AML) and T-ALL, merges PICALM to MLLT10. RT-PCR enabled identification of PICALM-MLLT10 and BCR-ABL1 e1-a2 fusion transcripts; in the context of chronic and acute myeloid leukemia, the latter usually has a monocytic presentation. We also identified overexpression of HOXA9, a gene essential to myeloid differentiation that is expressed in PICALM-MLLT10 and MLL-rearranged acute leukemias. This case fits with and extends a recently proposed multistage AML model in which constitutive activation of tyrosine kinases by mutations (BCR-ABL1) are associated with deregulation of transcription factors central to myeloid differentiation (HOXA9 secondary to PICALM-MLLT10).
Sindt
Audrey
A
Department of Biochemistry and Genetics, CHU Brabois, Nancy, France.
Deau
Benedicte
B
Brahim
Wajih
W
Staal
Anne
A
Visanica
Sorin
S
Villarese
Patrick
P
Rault
Jean-Philippe
JP
Macintyre
Elizabeth
E
Delabesse
Eric
E
D000293:Adolescent; D001853:Bone Marrow / Q000378:metabolism; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008677:Metaphase; D008957:Models, Genetic; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C092513:MLLT10 protein, human; D034041:Monomeric Clathrin Assembly Proteins; D015514:Oncogene Proteins, Fusion; C439003:PICALM protein, human; C511819:PICALM-MLLT10 fusion protein, human; D014157:Transcription Factors; C097899:homeobox protein HOXA9; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D016044:Fusion Proteins, bcr-abl