title: Clinical outcome and monitoring of minimal residual disease in patients with acute lymphoblastic leukemia expressing the MLL/ENL fusion gene.
abstract: We analyzed 12 MLL/ENL positive ALL patients consecutively diagnosed between 1999 and 2009. The MLL/ENL fusion was identified in 4/150 (2.6%), 8/993 (0.8%), and 0/70 of pediatric, adult, and elderly patients, respectively. Eight patients had a WBC count >50 × 10(9) /L. Ten cases had an evaluable immunophenotyping. A B or T precursor ALL occurred in 7 and 3 patients, respectively. Eleven/12 patients (92%) achieved CR. At 48 months, overall survival and event-free survival rates were 73.3% and 67%, respectively. At CR, a parallel RT-PCR evaluation of the MLL/ENL expression was available in 5 cases. Of these latter, 2 tested MLL/ENL-negative and 3 positive. The minimal residual disease molecular monitoring showed that MLL/ENL status did not correlate with outcome. In fact, all the 2 PCR-negative and 1 of the 3 PCR-positive cases relapsed. Further, a MLL/ENL expression, not preceding a relapse, was detected several times during the follow-up of five long-survivors. In conclusion, also in adults, the MLL/ENL fusion identifies a rare leukemic entity with a favorable prognosis. The observed inconsistency between the clinical cure and the presence of detectable MLL/ENL transcript suggests the existence of a MLL/ENL-expressing "preleukemia" stem cells, similar to what demonstrated for the AML1/ETO-positive leukemia setting.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Elia
authors.forename: Sara
authors.initials: S
authors.lastname: Grammatico
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoloni
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Angela
authors.initials: A
authors.lastname: Rago
authors.forename: Natalia
authors.initials: N
authors.lastname: Cenfra
authors.forename: Sergio
authors.initials: S
authors.lastname: Mecarocci
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Matteo
authors.initials: M
authors.lastname: Luciani
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Mabel
authors.initials: M
authors.lastname: Matarazzo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Moleti
authors.forename: Lidia
authors.initials: L
authors.lastname: Santoro
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D018365:Neoplasm, Residual / Q000175:diagnosis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D012074:Remission Induction; D012384:Rome; D016019:Survival Analysis; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C090862:ELL protein, human; C425207:MLL-ENL oncoprotein, human; D015514:Oncogene Proteins, Fusion; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein