Details

Autor(en) / Beteiligte

• CHILLON, Maria Carmen
• SANTAMARIA, Carlos
• BERNAL, Teresa
• DIAZ-MEDIAVILLA, Joaquin
• GARCIA DE COCA, Alfonso
• JESUS PENARRUBIA, Maria
• ANTONIO QUEIZAN, José
• GIRALDO, Pilar
• SAN MIGUEL, Jesús F
• GONZALEZ, Marcos
• GARCIA-SANZ, Ramón
• BALANZATEGUI, Ana
• SARASQUETE, Maria Eugenia
• ALCOCEBA, Miguel
• MARIN, Luis
• DOLORES CABALLERO, Maria
• BELEN VIDRIALES, Maria
• RAMOS, Fernando

Titel

Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients

Ist Teil von

• Haematologica (Roma), 2010-05, Vol.95 (5), p.745-751

Ort / Verlag

Pavia: Ferrata Storti Foundation

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Internal tandem duplications of the FLT3 gene (FLT3-ITDs) are frequent in patients with acute promyelocytic leukemia (APL), however its clinical impact remains controversial. We analyzed the prognostic significance of FLT3-ITD mutant level and size, as well as FLT3-D835 point mutations, PML-RARalpha expression and other predictive factors in 129 APL patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86) PETHEMA trials. FLT3-ITDs and D835 mutations were detected in 21% and 9% of patients, respectively. Patients with increased ITD mutant/wild-type ratio or longer ITD size displayed shorter 5-year relapse-free survival (RFS) (P=0.048 and P<0.0001, respectively). However, patients with D835 mutations did not show differences in RFS or overall survival (OS). Moreover, patients with initial normalized copy number (NCN) of PML-RARalpha transcripts less than the 25(th) percentile had adverse clinical features and shorter 5-year RFS (P<0.0001) and OS (P=0.004) compared to patients with higher NCN. Patients with low NCN showed increased incidence of ITDs (P=0.001), with higher ratios (P<0.0001) and/or longer sizes (P=0.007). Multivariate analysis showed that long FLT3-ITD (P=0.001), low PML-RARalpha levels (P=0.004) and elevated WBC counts (>10x10(9)/L) (P=0.018) were independent predictors for shorter RFS. We identified a subgroup of patients with high WBC, long FLT3-ITD and low NCN of transcripts that showed an extremely bad prognosis (5-year RFS 23.4%, P<0.0001). In conclusion, FLT3-ITD size and PML-RARalpha transcript levels at diagnosis could contribute to improve the risk stratification in APL.