FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia

Autor: Mariko Takenokuchi, Seiji Kawano, Yuji Nakamachi, Yasuyuki Sakota, Meilani Syampurnawati, Katsuyasu Saigo, Eiji Tatsumi, Shunichi Kumagai
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Hematology Reports, Vol 4, Iss 4, Pp e22-e22 (2012)
Druh dokumentu: article
ISSN: 2038-8322
2038-8330
DOI: 10.4081/hr.2012.e22
Popis: Acute promyelocytic leukemia (APL) is characterized by the specific PML-RARa fusion gene resulting from translocation t(15;17) (q22;q12). Internal tandem duplication (ITD) of the FLT3 gene has been observed in approximately 35% of APLs, and large-scale studies have identified the presence of ITD as an adverse prognostic factor for acute myeloblastic leukemia (AML) patients. Aberrant expressions of surface antigens, such as CD2, CD34, and CD56, have been found in APL, but the implications of this are not well understood. We investigated the incidence of the FLT3/ITD mutation and FLT3/D835 (I836) point mutation in 25 APL patients. Incidence ratios of FLT3/ITD, D835 (I836), and both FLT3/ITD and D835 (I836) were 36%, 36% and 8%, respectively. FLT3/ITD+ cases showed a predominance of the bcr3 isoform (P=0.008) and M3v morphology (P+ cases expressed CD2 (9 of 9) more frequently than that of FLT3/ITD- (1 of 16) (P+ cases (1 of 10, 10%) did not harbor FLT3/ITD, and all CD2+CD34+ cases (5 of 5, 100%) harbored FLT3/ITD. In addition, quantitative polymerase chain reaction analysis showed that FLT3 mRNA was more abundantly expressed in FLT3/ITD+ than that in FLT3/ITD- (P=0.025), while there was no difference between D835(I836)+ and D835(I836)- with regards to aberrant surface-antigen expression, expression levels of FLT3 mRNA, M3v morphology, and the bcr3 isoform of PML-RARa mRNA. This study demonstrates that the presence of FLT3/ITD, but not D835 (I836), is closely related to aberrant CD2 expression and high expression levels of FLT3 mRNA. Our findings also suggest that FLT3/ITD as a secondary genetic event may block differentiation at the immature stage of APL.
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