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

Acute promyelocytic leukemia (APL) is characterized by the specific PML-RARα 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...

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Main Authors:	Takenokuchi, Mariko, Kawano, Seiji, Nakamachi, Yuji, Sakota, Yasuyuki, Syampurnawati, Meilani, Saigo, Katsuyasu, Tatsumi, Eiji, Kumagai, Shunichi
Format:	Online
Language:	English
Published:	PAGEPress Publications 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555210/

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recordtype	oai_dc
spelling	pubmed-35552102013-01-25 FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia Takenokuchi, Mariko Kawano, Seiji Nakamachi, Yuji Sakota, Yasuyuki Syampurnawati, Meilani Saigo, Katsuyasu Tatsumi, Eiji Kumagai, Shunichi Article Acute promyelocytic leukemia (APL) is characterized by the specific PML-RARα 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<0.001). We found that all FLT3/ITD+ cases expressed CD2 (9 of 9) more frequently than that of FLT3/ITD− (1 of 16) (P<0.001), while only one of the CD2+ 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-RARα 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. PAGEPress Publications 2012-10-16 /pmc/articles/PMC3555210/ /pubmed/23355940 http://dx.doi.org/10.4081/hr.2012.e22 Text en ©Copyright M. Takenokuchi et al., 2012 This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Licensee PAGEPress, Italy
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Takenokuchi, Mariko Kawano, Seiji Nakamachi, Yuji Sakota, Yasuyuki Syampurnawati, Meilani Saigo, Katsuyasu Tatsumi, Eiji Kumagai, Shunichi
spellingShingle	Takenokuchi, Mariko Kawano, Seiji Nakamachi, Yuji Sakota, Yasuyuki Syampurnawati, Meilani Saigo, Katsuyasu Tatsumi, Eiji Kumagai, Shunichi FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
author_facet	Takenokuchi, Mariko Kawano, Seiji Nakamachi, Yuji Sakota, Yasuyuki Syampurnawati, Meilani Saigo, Katsuyasu Tatsumi, Eiji Kumagai, Shunichi
author_sort	Takenokuchi, Mariko
title	FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
title_short	FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
title_full	FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
title_fullStr	FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
title_full_unstemmed	FLT3/ITD associated with an immature immunophenotype in PML-RARα leukemia
title_sort	flt3/itd associated with an immature immunophenotype in pml-rarα leukemia
description	Acute promyelocytic leukemia (APL) is characterized by the specific PML-RARα 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<0.001). We found that all FLT3/ITD+ cases expressed CD2 (9 of 9) more frequently than that of FLT3/ITD− (1 of 16) (P<0.001), while only one of the CD2+ 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-RARα 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.
publisher	PAGEPress Publications
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555210/
_version_	1611949613158236160

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

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