PMID- 37597110
OWN - NLM
STAT- Publisher
LR  - 20231011
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 102
IP  - 11
DP  - 2023 Nov
TI  - Dominant-negative type of IKZF1 deletion showed a favorable prognosis in adult 
      B-cell acute lymphoblastic leukemia.
PG  - 3103-3113
LID - 10.1007/s00277-023-05405-0 [doi]
AB  - IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic 
      leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function 
      (LOF) deletions. The prognostic impact of each deletion has not been fully 
      elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 
      60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative 
      B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion 
      and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and 
      ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type 
      of deletion was not identified by the PCR, were categorized as "other." Patients 
      were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF 
      and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions 
      were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative 
      cases. LOF and other type IKZF1 deletions were found in 43.4% of 
      BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the 
      DN group showed significantly higher overall survival (OS) than that of the LOF 
      and other and WT groups (P = 0.011). Multivariate analysis including age, WBC 
      counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of 
      IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age >/= 65 
      (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of 
      IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion 
      showed better prognosis in adult B-ALL patients.Clinical trial registration This 
      study was part of a prospective observational study (Hokkaido Leukemia Net, 
      UMIN000048611). It was conducted in compliance with ethical principles based on 
      the Helsinki Declaration and was approved by the institutional review board of 
      Hokkaido University Hospital (#015-0344).
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Kimura, Hiroyuki
AU  - Kimura H
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Onozawa, Masahiro
AU  - Onozawa M
AUID- ORCID: 0000-0001-9267-2864
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan. 
      onozawa@med.hokudai.ac.jp.
FAU - Yoshida, Shota
AU  - Yoshida S
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Miyashita, Naoki
AU  - Miyashita N
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Yokoyama, Shota
AU  - Yokoyama S
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Matsukawa, Toshihiro
AU  - Matsukawa T
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Hirabayashi, Shinsuke
AU  - Hirabayashi S
AD  - Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
FAU - Goto, Hideki
AU  - Goto H
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
AD  - Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, 
      Sapporo, Japan.
FAU - Endo, Tomoyuki
AU  - Endo T
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
FAU - Oguri, Satoshi
AU  - Oguri S
AD  - Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, 
      Sapporo, Japan.
FAU - Fujisawa, Shinichi
AU  - Fujisawa S
AD  - Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, 
      Sapporo, Japan.
FAU - Mori, Akio
AU  - Mori A
AD  - Blood Disorders Center, Aiiku Hospital, Sapporo, Japan.
FAU - Kondo, Takeshi
AU  - Kondo T
AD  - Blood Disorders Center, Aiiku Hospital, Sapporo, Japan.
FAU - Hidaka, Daisuke
AU  - Hidaka D
AD  - Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
FAU - Okada, Kohei
AU  - Okada K
AD  - Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
FAU - Ota, Shuichi
AU  - Ota S
AD  - Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
FAU - Kakinoki, Yasutaka
AU  - Kakinoki Y
AD  - Department of Hematology, Asahikawa City Hospital, Asahikawa, Japan.
FAU - Tsutsumi, Yutaka
AU  - Tsutsumi Y
AD  - Department of Hematology, Hakodate Municipal Hospital, Hakodate, Japan.
FAU - Yamamoto, Satoshi
AU  - Yamamoto S
AD  - Department of Hematology, Sapporo City General Hospital, Sapporo, Japan.
FAU - Miyagishima, Takuto
AU  - Miyagishima T
AD  - Department of Hematology, Kushiro Rosai Hospital, Kushiro, Japan.
FAU - Hashiguchi, Junichi
AU  - Hashiguchi J
AD  - Department of Internal Medicine, Kitami Red Cross Hospital, Kitami, Japan.
FAU - Nagashima, Takahiro
AU  - Nagashima T
AD  - Department of Internal Medicine, Kitami Red Cross Hospital, Kitami, Japan.
FAU - Ibata, Makoto
AU  - Ibata M
AD  - Department of Hematology, Sapporo Kosei General Hospital, Sapporo, Japan.
FAU - Wakasa, Kentaro
AU  - Wakasa K
AD  - Department of Hematology, Obihiro Kosei Hospital, Obihiro, Japan.
FAU - Haseyama, Yoshihito
AU  - Haseyama Y
AD  - Department of Hematology, Tonan Hospital, Sapporo, Japan.
FAU - Fujimoto, Katsuya
AU  - Fujimoto K
AD  - Department of Hematology, National Hospital Organization Hokkaido Cancer Center, 
      Sapporo, Japan.
FAU - Ishihara, Toshimichi
AU  - Ishihara T
AD  - Department of Hematology, Kin-Ikyo Chuo Hospital, Sapporo, Japan.
FAU - Sakai, Hajime
AU  - Sakai H
AD  - Department of Hematology, Teine Keijinkai Hospital, Sapporo, Japan.
FAU - Teshima, Takanori
AU  - Teshima T
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Graduate 
      School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
AD  - Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, 
      Sapporo, Japan.
LA  - eng
GR  - 16K09836/Japan Society for the Promotion of Science/
GR  - 17K16174/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20230819
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
SB  - IM
OTO - NOTNLM
OT  - Acute lymphoblastic leukemia
OT  - Dominant-negative
OT  - Fluorescence in situ hybridization (FISH)
OT  - Hokkaido Leukemia Net (HLN)
OT  - IKAROS
OT  - IKZF1 deletion
EDAT- 2023/08/19 20:42
MHDA- 2023/08/19 20:42
CRDT- 2023/08/19 11:07
PHST- 2023/05/06 00:00 [received]
PHST- 2023/08/06 00:00 [accepted]
PHST- 2023/08/19 20:42 [pubmed]
PHST- 2023/08/19 20:42 [medline]
PHST- 2023/08/19 11:07 [entrez]
AID - 10.1007/s00277-023-05405-0 [pii]
AID - 10.1007/s00277-023-05405-0 [doi]
PST - ppublish
SO  - Ann Hematol. 2023 Nov;102(11):3103-3113. doi: 10.1007/s00277-023-05405-0. Epub 
      2023 Aug 19.