title: Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma.
abstract: L-type amino-acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki-67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie-Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high-risk MM.
authors.affiliation: Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Isoda
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Masanori
authors.initials: M
authors.lastname: Iwashina
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Morio
authors.initials: M
authors.lastname: Sawamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002869:Chromosome Aberrations; D005260:Female; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D027261:Fusion Regulatory Protein-1; D027283:Large Neutral Amino Acid-Transporter 1
keywords: CD98; L-type amino-acid transporter 1; melphalan; multiple myeloma; prognosis