Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9

• Published in: Genes chromosomes & cancer 2006-06, Vol.45 (6), p.575-582
• Main Authors: Sindt, Audrey, Deau, Benedicte, Brahim, Wajih, Staal, Anne, Visanica, Sorin, Villarese, Patrick, Rault, Jean-Philippe, Macintyre, Elizabeth, Delabesse, Eric
• Format: Article
• Language: English
• Subjects: Adolescent; Bone Marrow; Bone Marrow - metabolism; Cancer; fms-Like Tyrosine Kinase 3; fms-Like Tyrosine Kinase 3 - genetics; fms-Like Tyrosine Kinase 3 - metabolism; Follow-Up Studies; Fusion Proteins, bcr-abl; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Gene Expression Regulation, Neoplastic; Gene Fusion; Homeodomain Proteins; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Monocytic, Acute; Leukemia, Monocytic, Acute - genetics; Leukemia, Monocytic, Acute - metabolism; Life Sciences; Male; Metaphase; Models, Genetic; Monomeric Clathrin Assembly Proteins; Monomeric Clathrin Assembly Proteins - genetics; Monomeric Clathrin Assembly Proteins - metabolism; Oncogene Proteins, Fusion; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Phenotype; Transcription Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Translocation, Genetic
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.20320

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). © 2006 Wiley‐Liss, Inc.