CD34+CD38-CD58- Candidate Leukemia-Initiating Cells Are Clinically Relevant With The Unfavorable Prognosis In Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 354-354
Author(s):  
Yuan kong ◽  
Ying-Jun Chang ◽  
Yan-rong Liu ◽  
Ya-zhe Wang ◽  
Qian Jiang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Mrna Levels ◽  
Imatinib Resistance ◽  
Self Renewal ◽  
Philadelphia Chromosome Positive

Abstract Background The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has been greatly improved in the modern era of imatinib. Nevertheless, relapse is still a major cause of treatment failure in human Ph+ALL. Leukemia-initiating cells (LICs) are presumed to be responsible for relapse in leukemia. Therefore, we conducted a study to identify the candidate LICs that are responsible for disease progression and its clinical significance in patients with Ph+ALL. Aims To investigate the leukemia-initiating and self-renewal capacities of CD34+CD38-CD58- cells and determine the prognostic significance of CD34+CD38-CD58- phenotype in patients with Ph+ALL treated in Peking University Institute of Hematology. Methods The leukemia-initiating potential and self-renewal capacity of the sorted CD34+CD38-CD58-, CD34+CD38-CD58+,CD34+CD38+CD58- and CD34+CD38+CD58+ compartments were investigated in vivo using sublethally irradiated and anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice by intra-bone marrow–injection. Furthermore, we prospectively analyzed whether the identified CD34+CD38-CD58- compartment at diagnosis correlates with minimal residual disease (MRD) after therapy and clinical outcomes in 63 adult patients (18-60 years) with de novo Ph+ALL. Results Xenotransplantation of the sorted CD34+CD38-CD58- cells led to a repopulation of human B-ALL in primary and secondary recipient mice, which were phenotypically and clonally derived from the original Ph+ALL patients analyzed by flow cytometry, as well as quantitative real-time RT-PCR and fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities. Furthermore, the candidate CD34+CD38-CD58- LICs phenotype at diagnosis (n=16) significantly correlated with a lower complete remission rate and higher MRD frequency monitored by BCR-ABL mRNA levels in BM of Ph+ALL patients. Additionally, it directly correlated with higher cumulative incidence of relapse (CIR, 60% ± 1.97% vs. 15.51% ± 0.30%, P=0.002) and unfavorable disease-free survival (DFS, 33.75%±12.64% vs. 71.31%±7.17%, P=0.009) at 3-year. The CD34+CD38-CD58- group exhibited a higher rate of BCR-ABL mutations conferring higher level imatinib resistance than the other group (43.75% vs. 17.02%, P=0.04). Multivariate analyses revealed that CD34+CD38-CD58- phenotype at diagnosis was an independent risk factor for relapse (HR=4.35, P=0.009) and DFS (HR=3.38, P=0.008) in adult Ph+ALL. Summary/Conclusion Both the xenotransplantation data as well as the clinical correlation studies show that CD34+CD38-CD58- compartment enrich for leukemia-initiating cells in adult Ph+ALL. CD34+CD38-CD58- phenotype at diagnosis independently correlates with an adverse prognosis, which promises to be an efficient tool for relapse prediction and risk-stratification treatment in adult Ph+ALL patients. Acknowledgments This work was supported by grants from National Natural Science Foundation of China (grants no. 30800483&81230013) and Beijing Municipal Science and Technology Program (grant no.Z111107067311070). Disclosures: No relevant conflicts of interest to declare.

scholarly journals First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia

Blood ◽  
2010 ◽  
Vol 116 (12) ◽  
pp. 2070-2077 ◽  
Author(s):  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Deborah Thomas ◽  
Stefan Faderl ◽  
Dan Jones ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Clinical Activity ◽  
High Dose ◽  
Newly Diagnosed ◽  
Imatinib Resistance ◽  
Philadelphia Chromosome Positive

AbstractThe combination of cytotoxic chemotherapy and imatinib has improved the outcome for patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib has significant clinical activity in patients with imatinib resistance. We examined the efficacy and safety of combining chemotherapy with dasatinib for patients with Ph+ ALL. Newly diagnosed patients received dasatinib 50 mg by mouth twice per day (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyper-CVAD, and high-dose cytarabine and methotrexate. Patients in complete remission received maintenance daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. Thirty-five patients with untreated Ph+ ALL with a median age of 53 years (range, 21-79 years) were treated; 33 patients (94%) achieved complete remission. Two patients died of infections before response assessment. Grade 3 and 4 adverse events included hemorrhage and pleural and pericardial effusions. With a median follow-up of 14 months (range, 4-37 months), the median disease-free survival and median overall survival have not been reached, with an estimated 2-year survival of 64%. The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793.

scholarly journals P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

2021 ◽  
pp. 1040-1050
Author(s):  
Samah Kohla ◽  
Sarah EL Kourashy ◽  
Zafar Nawaz ◽  
Reda Youssef ◽  
Ahmad Al-Sabbagh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Rare Case ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Cytogenetic Abnormality ◽  
Rare Case Report ◽  
Philadelphia Chromosome Positive

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

Curcumin Potentiates Antitumor Activity of Imatinib Via Inhibition of the AKT/mTOR Signaling Pathway and Down-Regulation of Bcr-Abl Gene in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3559-3559
Author(s):  
Yuping Gong ◽  
Yong Guo ◽  
Ting Niu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Mtor Signaling ◽  
Perennial Herb ◽  
Apoptosis Protein ◽  
Philadelphia Chromosome Positive

Abstract Abstract 3559 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is triggered by constitutively activated BCR-ABL and SRC family tyrosine kinases. They interact each other, then activate downstream growth-signaling pathways including Raf/MEK/ERK,Akt/mTOR and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for Ph+ leukemia. However, response rate of Ph+ ALL to imatinib is low, relapse is frequent and quick. Studies have documented the potential anti-tumor activities of curcumin, a yellow colored polyphenol from the perennial herb Curcuma longa. However, whether curcumin can be used in the therapy for Ph+ALL remains obscure. Here, we reported that curcumin induced autophagic cell death by activating RAF/MEK/ERK pathway in early stage of the 24-hour exposure course, later induced apoptosis by inhibiting AKT/mTOR, ABL/STAT5 signalings, down-regulating expression of bcr/abl gene and Bcl2 anti-apoptosis protein, and up-regulating the expression of pro-apoptosis protein BAX in Ph+ALL cell line SUP-B15. Furthermore, we found curcumin exerted synergetic anti-leukemia effect with imatinib by inhibiting imatinib-mediated up-regulation of the activation of AKT/mTOR signaling and down-regulating expression of bcr/abl gene. It is worth noting that curcumin provide advantages over dexmethasone as to synergetic anti-leukemia effect with imatinib because dexmethasone improved the imatinib-mediated up-regulation of the activation of AKT/mTOR/P70S6 signaling. In primary samples from Ph+ALL patients, curcumin inhibit growth signaling not only in newly-diagnosised patient but also in imatinib-resistant patient. Moreover, curcumin effectively exhibited anti-leukemia efficacy and synergetic anti-leukemia effect with imatinib in Ph+ALL mouse models. These results demonstrate that curcumin may be a promising agent for the treatment of patients with Ph+ ALL, and curcumin might be particularly effective when used with current induction regimens consisting of imatinib with or without chemotherapy for treating Ph+ ALL. [Grant Support:National Natural Science Foundation of China (No.30770912), Foundation of the Science & Technology Department of Sichuan Province (No.2008SZ0017)]. Disclosures: No relevant conflicts of interest to declare.

Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome–positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1408-1413 ◽  
Author(s):  
Adrienne de Labarthe ◽  
Philippe Rousselot ◽  
Françoise Huguet-Rigal ◽  
Eric Delabesse ◽  
Francis Witz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Free Survival ◽  
Prospective Trials ◽  
Polymerase Chain ◽  
Philadelphia Chromosome Positive

AbstractThe combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.

Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia (ALL) Treated with Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1527-1527
Author(s):  
Michael E. Rytting ◽  
Deborah A. Thomas ◽  
Elias Jabbour ◽  
Anna R.K. Franklin ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Adolescent And Young Adult ◽  
Days Of Therapy ◽  
Grade Iii

Abstract Abstract 1527 Several pediatric-based protocols for treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults have been completed or are ongoing. Some studies have enrolled patients (pts) up to age 55 years, and, so far, results have been satisfactory. Augmented Berlin-Frankfurt-Muenster (ABFM) has been shown to be an effective and tolerable treatment for ALL in adolescents. To evaluate the efficacy and toxicity of this therapy in young adults, we designed a protocol of modified ABFM therapy for pts with ALL from age 12 to 40 years old. 83 pts have been enrolled on protocol and are evaluable for toxicity. 68 pts with de novo Philadelphia chromosome negative ALL have completed at least 29 days of therapy (induction) on protocol. They have the following characteristics: 56 (82%) pts have pre-B ALL and 12 (18%) have T-ALL. The median age is 21 (mean=23; range=13–39). The median presenting WBC=5.3 (mean=32; range= 0.4–494). 65/68 (96%) pts have achieved a remission. One patient died during induction. 50 (74%) pts have attained remission by 15 days of induction, while 15 (22%) have been slow responders. 5/68 (7%) pts have required an extension of induction by 2 weeks. At day 29 of therapy, 38 (56%) pts had negative minimal residual disease (MRD) by flow cytometry, 20 (29%) patients were positive for MRD, 10 were suspicious or not available. By day 84 of therapy, 49 (72%) pts were negative for MRD and 9 (13%) were positive. Currently, there have been 17 relapses and 10 deaths. Toxicities in the entire group include severe asparaginase allergy in 15 (18%) pts, thrombus formation in 16 (19%) pts, hyperbilirubinemia grade III-IV in 19 (23%) pts, ALT/AST grade III-IV in 23 (28%) pts, CNS stroke-like symptoms in 6 (7%) pts, hypofibrinogen grade III-IV in 26 (31%), pancreatitis in 6 (7%), and avascular necrosis in 6 (7%) pts. Hepatic toxicity has resolved completely within two weeks in almost all pts as has the CNS toxicity. In summary, induction success, by morphology and flow cytometry, has been satisfactory with this regimen. CRD and OS have not been significantly better than with HyperCVAD therapy for this age group. Expected toxicities have been prominent, but mostly transient. Hypofibrinogenemia is frequent, but bleeding is rare. Thrombosis and severe allergic reactions are more frequent than in pediatric trials. For pts 25 years of age and younger, the overall survival (OS) and disease free survival (DFS) at 2 years are 88% and 84% respectively. For pts > 25 years of age, the OS and DFS at two years are 65% and 50% respectively. This difference in OS between the groups is statistically significant. Continued enrollment is anticipated to further evaluate the survival differences between these two patient groups. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Poor Outcome of CRLF2 Rearranged Philadelphia Negative Acute Lymphoblastic Leukemia Adults Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5290-5290 ◽  
Author(s):  
Yasser H Elnahass ◽  
Omar A Fahmy ◽  
Mohamed Abdel Mooti Samra ◽  
Fatma A Elrefaey ◽  
Mahmoud T Bokhary ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Bone Marrow Aspiration ◽  
Poor Outcome ◽  
Egyptian Patients ◽  
Diagnostic Work

Abstract BACKGROUND: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph'-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1 positive ALL and a poor outcome. Rearrangements of cytokine receptor like factor 2 (CRLF2) are identified in approximately 50% of Ph'-like and 10% of B-other ALL patients. AIM: To identify the incidence of CRLF2 rearrangements and the frequency of relapse in a cohort of B-other Precursor B-ALL adults Egyptian patients who were treated with conventional therapy at National Cancer Institute, Cairo University. METHODS: The routine diagnostic work-up at diagnosis included Bone marrow aspiration, immunophenotyping, karyotyping, fluorescent in situ hybridization (FISH) for BCR-ABL1 and KMT2A (MLL) and CRLF2 rearrangements (IGH-CRLF2 or P2RY8-CRLF2), and molecular analyses of BCR-ABL1 translocations. Patients within the age group 18-25 years received Total XV protocol while patients >25 years received Hoelzer's protocol. RESULTS: Forty patients were included (22 males, 18 females). Median age at diagnosis was 25 years (18 -65). Median TLC was 14.9 x109/L (1.1 - 201), median Hb was 9.9 gm/dl (5-12.9), median platelet count was 47 x 109/L (19-359) and median BM blasts count was 90% (30-100). CRLF2 rearrangement was detected in 4/40 (10%) patients. All CRLF2 positive patients (100%) relapsed at 6 months vs. 11/36 (30%) CRLF2 negative (p<0.001). At 6 months follow up, disease free survival (DFS) was 70% in CRLF2 negative patients vs. 0% in CRLF2 rearranged (p=0.04). At 1 year follow up, overall survival (OS) was 30 (75%) for CRLF2 negative vs. 0 (0%) for CRLF2 positive patients (p=0.01). CONCLUSION: CRLF2 rearrangements constitute a high risk independent prognostic factor in adult precursor B-ALL patients denoting a poor outcome and should be studied in ALL Ph' negative patients. Additional TKI therapy should be included for this category of patients in our protocols to improve outcome. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Imatinib Plus Vincristin & Prednisolone Induces Complete Remission and Prolonged Survival in Elderly Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4339-4339
Author(s):  
Ashis Mukhopadhyay ◽  
Soma Mukhopadhyay ◽  
Pinaki Ranjan Gupta ◽  
Ujjal Kanti Roy ◽  
Ajoy Sinha
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Induction Treatment ◽  
Molecular Testing ◽  
Molecular Response ◽  
Highly Active ◽  
Philadelphia Chromosome Positive

Abstract Introduction: Acute lymphoblastic Leukemia (ALL) in elderly patients (50yrs or older) carries a poor prognosis. In survival studies using in variety of therapeutic regimens. This may be because of relatively high frequency of the Philadelphia chromosome (Ph). With the advent of dose intensive chemotherapy regimen such as hyper CVAD (Fractionated Cyclophosphamide, Vincristin, Doxorubicin, Dexamethasone) overall survival has not improved. The aim of our study was to see the effectiveness of Imatinib plus Vincristin & Prednisolone in Philadelphia Chromosome positive in elderly acute lymphoblastic leukemia patients. Material & Methods: During period from January 2006 December 2006 we selected 10 consecutive elderly (more than 50yrs) Ph+ ALL patients in the haemato-oncology department Netaji Subhash Chandra Bose Cancer Research Institute. There were 4 males & 6 females. The median age of the patient was 64years (range 51 to 77yrs). All patients were started with Imatinib mesylate (Natco pharma) 400mg daily. Prednisolone was given 40mg /m2 over 6weeks & followed by 2weeks tapering dose. Vincristin was given 2mg/m2 weekly for 6weeks. All patients were evaluated by bone marrow and molecular testing done every 3monthly for 1year then 6monthly. Result: All patients (100%) obtained complete haematological & partial molecular response at 3month. Three patient (30%) achieved complete molecular response at 9month. With median follow-up of 8months (range 6–15months) the disease free survival and overall survival were 80% & 90% respectively. Most of the induction treatment was done as OPD basis, no hospitalization required. The therapy was tolerated well. Conclusion: We concluded that Imatinib plus Vincristin & Prednisolone is a feasible, highly active protocol for elderly Philadelphia Chromosome positive acute lymphoblastic leukemia patients. It is well tolerated & associated with good quality of life.

Characteristics and Prognostic Significance of CRLF2 High Expression and the Co-Existence with JAK1 Mutations and Ikaros Deletion in Adult Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3800-3800 ◽  
Author(s):  
Zheng Ge ◽  
Juan Liu ◽  
Run Zhang ◽  
Xing Guo ◽  
Jing-Yan Xu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Point Mutations ◽  
High Expression ◽  
Newly Diagnosed

Abstract Objective Cytokine receptor-like factor 2 (CRLF2) play an important role in differentiation and proliferation of lymphoid precursor cells through activation of JAK signaling pathway. Increased CRLF2 expression associates with mutations in JAK2, a combination that transforms hematopoietic cells, suggesting that mutants in JAK family members and CRLF2 may cooperate to contribute to acute lymphoblastic leukemia (ALL) pathogenesis. Moreover, the Ikaros deletion is also associated with the development of T-/B-cell ALL with poor outcome and relapse of high-risk leukemia. The aim of this study was to determine the clinical characterization and prognostic values of CRLF2 high expression and its concomitant expression with JAK1 mutations and Ikaros deletion in adult ALL patients. Methods Quantitative PCR (qPCR) was performed to detect the expression of CRLF2 in 133 newly diagnosed adult patients with ALL. Genomic DNA was amplified to detect the mutations of the exon 13, 14, 16, 18 and 19 of JAK1, and IKZF1 exons 4 through 7 deletions (△4–7) by direct sequencing or sequencing after cloning. The CD34, CD13, CD33 and other markers were detected on the leukemia cells from bone marrow of the patients by flow cytometry, and the correlations of the CRLF2 high expression with the clinical features, survival, and with co-expression of JAK1 mutations and Ikaros deletion were statistically analyzed with Pearson's chi-square test or Fisher's exact test and Kaplan–Meier curves analysis. Results CRLF2 high expression was detected in 22.8% of newly diagnosed adult ALL. The patients with CRLF2 high expression has significantly higher percentage of CD34, CD13 or CD33 positive than those with low expression（91.3% vs 62%, P=0.008; 76.2% vs 46.3%, P=0.016; 80.0% vs 37.9%, P=0.001), higher frequency of splenomegaly（60.0% vs 32.0%, P=0.040) in the adult ALL and shorter overall survival and event-free survival（9.5 months vs 16 months, P=0.029; 3 months vs 9 months, P=0.030）in the Philadelphia chromosome negative ALL. Moreover, the 4 JAK1 point mutations with amino acid changes were detected in the patients, which had significant CRLF2 high expression compared to that without mutation（75% vs 21.3%, P=0.037). The co-existence of CRLF2 high expression and IKZF1 exons 4-7 deletion (isoform Ik6) was found in 4 of 10 patients. Conclusion CRLF2 high expression predicts poor survival, and significantly co-exists with JAK1 mutation and Ikaros deletion in adult ALL patients. Our result also suggested that CRLF2, JAK1 and IKZF1 could be integrated in future prognostic model of adult ALL as possible markers for high-risk leukemia. Disclosures No relevant conflicts of interest to declare.

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