IKZF1 alterations and expression of CRLF2 predict prognosis in adult Chinese patients with B-cell precursor acute lymphoblastic leukemia

Fang, Qiuyun; Zhao, Xingli; Li, Qinghua; Li, Yan; Liu, Kaiqi; Tang, Kejing; Wang, Ying; Liu, Bingcheng; Wang, Min; Xing, Haiyan; Rao, Qing; Tian, Zheng; Wang, Jianxiang; Mi, Yingchang

doi:10.1080/10428194.2016.1180682

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…For example, IKZF1 deletion, a hallmark of high-risk pediatric ALL, is related to poor prognosis in adult ALL ( 4 – 10 ). This phenomenon was consistent with our previous study, wherein IKZF1 deletion was associated with poor survival in adult B-ALL patients ( 11 , 12 ).…”

Section: Introductionsupporting

confidence: 94%

Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia

et al. 2021

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Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.

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Section: Introductionsupporting

confidence: 94%

Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia

et al. 2021

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“…As mentioned earlier, patients with IKZF1 gene deletions did not exhibit a poor prognosis in the present study, which may be attributed to the small sample size and short follow-up duration. In addition, it was revealed that MLPA was less sensitive than PCR in analyzing the IKZF1 gene deletions, which may result in an increased number of false negative cases and may influence the prognostic significance of such observations (8).…”

Section: Discussionmentioning

confidence: 99%

“…51104; Qiagen GmbH, Hilden, Germany) was used for DNA extraction, according to the manufacturer's protocols. TRIzol™ (Life Technologies; Thermo Fisher Scientific, Inc., Waltham, MA, USA) was used to extract RNA, RNA was also extracted from the MNCs of 50 patients (MNCs <10 6 , as dictated by the TRIzol protocol) and was synthesized into cDNA, as previously described (8). Nested reverse transcription polymerase chain reaction (RT-PCR) was performed, as previously described (PCR Master mix; Takara Biotechnology Co., Ltd., Dalian, China) (8).…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of copy number alterations detected by multi‑link probe amplification of multiple genes in adult acute lymphoblastic leukemia

Fang

Tian

et al. 2018

Oncol Lett

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Abstract. The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), ETS variant 6 (ETV6), RB transcriptional corepressor 1 (RB1), BTG anti-proliferation factor 1 (BTG1), early B-cell factor 1 (EBF1), cyclin dependent kinase inhibitor 2A/2B (CDKN2A/2B) and cytokine receptor like factor 2 (CRLF2) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed. Gene deletions were detected in 58/87 (66.7%) ALL patients. The most common deletions were observed in the following genes: IKZF1 (40.6%), CDKN2A (31.9%), CDKN2B (29%), PAX5 (21.7%), RB1 (14.5%) and BTG1 (10.1%). B cell-ALL (B-ALL) patients with CDKN2A/2B deletions exhibited poor 2-year overall survival (OS; P=0.055) and relapse-free survival (RFS; P=0.054) rates. CDKN2A/2B deletions were associated with poor 2-year OS (P=0.045) and RFS (P= 0.071) rates in Philadelphia chromosome positive (Ph

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“…Some studies have shown an association between CRLF2 overexpression and adverse prognosis, whereas others have demonstrated a correlation between P2RY8 ‐ CRLF2 and an inferior outcome. The prognostic value of CRLF2 overexpression and P2RY8 ‐ CRLF2 in B‐ALL with different risk features, particularly intermediate‐ and low‐risk B‐ALL, has not yet been well established 14–16 . Furthermore, it has been reported that the abnormal expression of CRLF2 is not suggestive of poor prognosis in B‐ALL 17 .…”

Section: Discussionmentioning

confidence: 99%

Effects of different aberrations in the CRLF2 gene on the biological characteristics and drug sensitivities of Nalm6 cells

Jia

et al. 2020

Int J Lab Hematology

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Introduction To investigate the effects and mechanism of action of upregulated CRLF2 expression resulting from different aberrations in the CRLF2 gene (CRLF2, CRLF2 + IK6, P2RY8‐CRLF2 and CRLF2 F232C) in the B cell ALL cell line Nalm6. Methods Cell proliferation was measured using cell counting kit‐8. Transcriptome sequencing technology (RNA‐seq) was used to compare changes in gene expression resulting from different aberrations in CRLF2. High‐throughput drug sensitivity testing was used to determine the drug sensitivity of cells. Results All four aberrations in CRLF2 upregulated CRLF2 expression and promoted the proliferation of Nalm6 cells. The RNA‐seq results showed the upregulation of genes in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and the downregulation of genes in the cell cycle pathway in the CRLF2 F232C‐overexpressing cells. Western blotting showed that the expression of p‐STAT5 protein was significantly higher in the CRLF2 F232C‐overexpressing cells. Cells with aberrations in CRLF2 were more resistant to cyclophosphamide and drugs commonly used during treatment than cells in the vector group. The half‐maximal inhibitory concentration (IC50 or GI50) of dexamethasone was significantly higher in the CRLF2 F232C‐overexpressing cell line. Conclusions The overexpression of CRLF2, CRLF2 + IK6, P2RY8‐CRLF2 and CRLF2 F232C promotes the proliferation of Nalm6 cells, activates the JAK/STAT signalling pathway and leads to a reduction in sensitivity towards various chemotherapeutic drugs.

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IKZF1 alterations and expression of CRLF2 predict prognosis in adult Chinese patients with B-cell precursor acute lymphoblastic leukemia

Cited by 14 publications

References 21 publications

Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia

Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia

Prognostic significance of copy number alterations detected by multi‑link probe amplification of multiple genes in adult acute lymphoblastic leukemia

Effects of different aberrations in the CRLF2 gene on the biological characteristics and drug sensitivities of Nalm6 cells

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