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Background: Polycythemia vera (PV) is the most common type of Philadelphia-negative myeloproliferative neoplasms (MPNs). PV is a long-term debilitating and life-threatening cancer that is associated with the risk of thrombosis, hemorrhage, and a long-term risk of developing myelofibrosis and acute myeloid leukemia. Early intervention with a disease-modifying treatment that can eradicate the mutated clones is needed to prevent disease progression and transformation. To date, therapeutic options for PV are limited and they only address the signs and symptoms. Most low-risk patients with PV are treated with phlebotomy and low-dose aspirin to manage increased blood viscosity and reduce the risk of vascular events, whereas high-risk and certain low-risk patients are treated with cytoreductive agents. Several cytoreductive agents are available such as hydroxyurea (HU) which is commonly used as a first-line therapy. Ruxolitinib, a JAK2 inhibitor, is also used. While interferon alfa agents have been used off label in clinical practice for more than three decades, their use has been limited due to the tolerability concerns. Ropeginterferon alfa-2b (P1101), a long-acting, mono-pegylated proline interferon, was developed for the treatment of MPNs, including PV. The novel formulation of P1101 improves its pharmacokinetic properties allowing treatment every 2 weeks with improved tolerability and convenience. P1101 was evaluated for the treatment of PV in the phase 3 PROUD-PV trial and its extension study CONTINUATION-PV. In the PROUD-PV study, due to the slow P1101 titration schedule, the maximum P1101 dose was not reached until week 28 and the primary analysis was done at 52 weeks. In CONTINUATION-PV, when patients were on their effective doses, a significantly higher proportion of patients treated with P1101 achieved a complete hematologic response (CHR) with improved disease burden compared to HU-treated patients. At 48 months there was a significant reduction in allelic burden from a baseline of 37.3% to 9.8% with 13.8% of patients achieving a complete molecular response (CMR). The molecular response rates (complete + partial) at 60 months was 69.1%. P1101 was approved by the European Medicines Agency in 2019 and the Taiwan Food and Drug Administration in 2020 as monotherapy in adults for the treatment of PV without symptomatic splenomegaly. Here, we describe a phase 2 study of P1101 in Chinese patients with PV utilizing an accelerated P1101 dose titration schedule. Study Design and Methods: This phase 2, multicenter, single-arm study is designed to evaluate safety and efficacy of P1101 in Chinese patients with PV utilizing a 250-350-500 ug P1101 dose titration schedule. The primary analysis will be conducted at 24 weeks. The study will recruit approximately 49 subjects in 15-20 sites in China. Key eligibility criteria include diagnosis of PV according to the 2016 WHO criteria, and resistance or intolerance to prior HU according to 2020 guidelines of CSCO. Patients who previously received interferon therapy have to be anti-P1101 binding antibody negative during the screening visit to be eligible. The study excludes patients with symptomatic splenomegaly. Eligible patients receive subcutaneous administration of P1101. Patients will receive an initial dose of 250 µg at Week 0, 350 µg at Week 2, and then 500 µg at Week 4. The dose is maintained at the highest dose that can be tolerated and delivers the best disease response. The maximum recommended dose is 500 μg every 2 weeks. Low-dose aspirin is administered during the 52 weeks of study treatment, unless contraindicated. The primary efficacy endpoint is the phlebotomy-free CHR rate at Week 24. Secondary endpoints include changes in hematocrit, white blood cell count, platelet count; time requiring no phlebotomy; time to first response; and duration of response. All patients will continue receiving treatment until week 52 to provide long-term follow-up information (blood parameters, molecular and cytogenetic data, safety parameters, and optional bone marrow data). This study has been granted IND approval by China CDE on Apr2021. Recruitment is expected to begin in early September 2021 with trial results expected in Q3 2022. Figure ： Study Design Figure 1 Figure 1. Disclosures Zagrijtschuk: PharmaEssentia U.S.A. Corp.: Current Employment. Urbanski: PharmaEssentia Corporation: Current Employment. Qin: PharmaEssentia Corp.: Current Employment.

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation–seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

Leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) is associated with a poor prognosis and resistance to therapy. Although previous candidate genetic studies have identified mutations in MPN patients who develop acute leukemia, the complement of genetic abnormalities in MPN patients who undergo LT is not known nor have specific molecular abnormalities been shown to have clinical relevance in this setting. We performed high-throughput resequencing of 22 genes in 53 patients with LT after MPN to characterize the frequency of known myeloid mutations in this entity. In addition to JAK2 and TET2 mutations, which occur commonly in LT after MPN, we identified recurrent mutations in the serine/arginine-rich splicing factor 2 (SRSF2) gene (18.9%) in acute myeloid leukemia (AML) transformed from MPNs. SRSF2 mutations are more common in AML derived from MPNs compared with LT after myelodysplasia (4.8%) or de novo AML (5.6%), respectively (P = .05). Importantly, SRSF2 mutations are associated with worsened overall survival in MPN patients who undergo LT in univariate (P = .03; HR, 2.77; 95% CI, 1.10-7.00) and multivariate analysis (P < .05; HR, 2.11; 95% CI, 1.01-4.42). These data suggest that SRSF2 mutations contribute to the pathogenesis of LT and may guide novel therapeutic approaches for MPN patients who undergo LT.

Abstract 2802 Background: Therapy-related myelodysplastic syndromes and acute myelogenous leukemia (tMDS/AML) comprise a poor-risk subset of MDS/AML and are associated with a higher rate of cytogenetic abnormalities and complex karyotypes. Large scale mutation profiling efforts in de novo MDS have identified mutations that correlate with clinical features but such mutations have not been investigated in tMDS/AML. Methods: Cryopreserved (mononuclear cell fractions) bone marrow and peripheral blood samples from tMDS/AML patients were analyzed. Lymphocytes were depleted from these fractions by either fluorescence-activated cell sorting or affinity column selection. Genomic DNA was subjected to high throughput PCR and sequenced for TP53, TET2, DNMT3a, ASXL1, IDH1, IDH2, SF3B1, EZH2, EED, SUZ12, and RBBP4. Somatic mutations were validated by comparison to lymphocyte DNA controls. Patient selection was based on sample availability for tMDS/AML patients with untreated or active, previously treated disease. Results were correlated with clinical outcomes, cytogenetic profiles, and response to therapy. Results: Samples from 38 patients (20 males, 18 females) with tMDS/AML were analyzed. For their primary malignancy (≥ 2 malignancies, n=3; AML, n=1; breast, n=4; colorectal, n=3; Hodgkins or composite lymphoma, n=3; gastric, n=1; melanoma, n=2; NHL, n=12; ovarian, n=1; prostate, n=3; sarcoma, n=2; thyroid, n=3), patients received chemotherapy alone (n=17), radiation alone (n=4), radioactive iodine alone (n=1), chemotherapy plus radiotherapy (n=13), radiotherapy plus radioactive iodine (n=1), chemotherapy plus radiotherapy plus radioactive iodine (n=2). Median latency time between primary malignancy treatment and MDS diagnosis date was 5.68yrs (range, 0.71–30.88). Median age at MDS diagnosis was 65yrs (range, 34–83). Not surprising was the finding that of the 35 MDS patients with complete IPSS parameter data most were IPSS Int-2 (45%) or High Risk (13%) compared to Low (11%) or Int-1 Risk (24%) disease, and in contrast to expected proportions at diagnosis for de novo MDS. WHO Classifications were: RA, n=3; RCMD, n=11; RAEB-1, n=7; RAEB-2, n=7; AML, n=3; CMML-1, n=1; MDS-U, n=3; Unknown, n=3. The median survival was 16.8mo. Median time between MDS diagnosis and sample procurement was 3.0mo (range, 0–57.2) during which 2 patients progressed to AML, 11 received a DNA methyltransferase inhibitor (DNMTI), 1 induction chemotherapy, and 2 DNMTI plus induction. We identified somatic mutations in 15/38 (39.5%) patients. Including cytogenetic abnormalities, we identified somatic alterations in 34/38 (88%) of the patients in this cohort. TP53 mutations were most common, detected in 8/38 (21%) patients, followed by TET2 in 4/38 (10.5%), DNMT3a in 3/38 (7.9%), ASXL1 in 1/38 (2.6%), IDH1 in 1/38 (2.6%), and EZH2 in 1/38 (2.6%). No IDH2, SF3B1, EED, SUZ12, or RBBP4 mutations were detected. Only 2 patients had concurrent point mutations (one patient with TP53/TET2/DNMT3 mutations and one patient with TET2/EZH2 mutations). 7/38 (18.4%) patients had TP53 loss by FISH analysis or exhibited loss of chromosome 17/17p; 2 of these patients showed concurrent TP53 point mutations consistent with biallelic TP53 loss. 12/13 patients with TP53 abnormalities (point mutations, loss of TP53 by FISH, or loss of chromosome 17) had IPSS Poor Risk cytogenetics and 11/13 patients had abnormalities in chromosome 5 (del 5q or monosomy 5). In patients without TP53 abnormalities, 9/25 had Poor Risk cytogenetics and 5/25 had abnormalities in chromosome 5. The median survival for patients with TP53 abnormalities was 9.7mo compared to 64.4mo for patients with no TP53 abnormalities (p=0.0043). Of the 13 patients with TP53 abnormalities, 12 received treatment for tMDS/AML. 3/12 were refractory to the first line of therapy, and 7 were unable to receive an adequate course of therapy with hypomethylating agents due to toxicity or progressive disease. Conclusions: TP53 point mutations are more common in tMDS/AML than in de novo MDS (7.5%, Bejar et al) while incidence of TET2 and ASXL1 mutations were lower in tMDS/AML compared to de novo MDS (20.5% and 14.4%, respectively). TP53 and TET2 point mutations were more strongly associated with exposure to prior chemotherapy, but not with exposure to radiation therapy. Taken together, these data demonstrate that TP53 mutations are common in tMDS/AML and are correlated with adverse clinical outcomes. Disclosures: No relevant conflicts of interest to declare.

Abstract 3379 Background: The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation of Abl kinase domain, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. Methods: We identified 26 untreated CML patients (UCML), 33 patients treated with imatinib at daily doses of 300–800 mg, and 18 healthy volunteers. 14 patients were resistant to imatinib. Routine cytogenetic analysis was performed in patients. In the resistant patients, ABL kinase domain mutations were detected. High-quality genomic DNA was processed in accordance with the genomic mapping 250K NspI protocol and hybridized to 250K NspI SNP arrays according to the manufacturer's instructions in 9 patients treated with imatinib. Gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was utilized for the measurement of the small molecular weight endogenous compounds. The metabolic phenotypes of CML patients, and the responses of CML to imatinib were characterized by means of GC/TOFMS based metabonomic technique. Results: Mutations were detected in only 1 BC patient (L232P, F336L, and C349R). A total of 44 deletions, 2 duplication, and 7 regions of loss of heterozygosity (LOH) were identified by SNP array analysis. In addition to sex chromosome, four of 6 CP RCML patients did not show other abnormal genome. Deletions, duplication and LOH on chromosome 17, 9, 22, 5 and 19 were identified in several important chromosomal regions of BC patients. The untreated CML patients (UCML) showed different metabolic pattern from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. Some amino acids, such as glutamate, ornithine, glycine, and pyroglutamate, were found at higher levels in UCML compared with those in HC, which indicates a cellular requirement for a higher turnover of structural proteins. After imatinib treatment, patients sensitive to imatinib (SCML) and patients resistant to imatinib (RCML) had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA). In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. Taken together, it strongly suggested that metabolic variation between BC and CP patients were closely related to genomic alterations. Conclusion: We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients sensitivity or resistance to drug intervention. Disclosures: No relevant conflicts of interest to declare.

Abstract 2187 Poster Board II-164 Chronic myeloid leukemia (CML) progression is characterized by occurrence of new cytogenetic and molecular abnormalities. In the previous study, we have shown the important role of GATA-2 L359V mutation in CML progression. To further ascertain the truth of transcription factor GATA-2 in hematological malignancies, we expanded our study to GATA-2 full length by directly sequencing and applied MassARRAY assay into GATA-2 L359V mutation analysis. Finally, no GATA-2 L359V mutation was found in 270 acute myeloid leukemia, 30 myelodysplastic syndrome, 50 acute lymphoblastic leukemia, 12 chronic lymphocytic leukemia, 40 CML chronic phase and 286 BCR/ABL negative myeloproliferative disorders except CML blast crisis. A new variation of GATA-2 resulted in P250A change was identified, which was not found to have statistical difference between patients with hematological malignancies and healthy control. Hence, we concluded GATA-2 L359V is exclusively associated with CML progression but not other hematological malignancies and P250A is a new single nucleotide polymorphism. Disclosures: No relevant conflicts of interest to declare.

Abstract 4989 Introduction Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN). Methods To ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients, we applied Allele-Specific Polymerase Chain Reaction (AS-PCR), directly sequencing and MassARRAY assay into our study. Results The positive rate of JAK2 V617F in polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% individually. We also found one ET patient, two PMF patients harboring MPL W515L mutation, and three PV patients harboring JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Moreover, clinical data demonstrated that PV patients with JAK2 exon 12 mutations had higher hemoglobin and lower age as well as WBC than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype was not found to have significant difference among PV, ET and PMF patients either. Conclusion We conclude that JAK2 V617F is major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients. Disclosures No relevant conflicts of interest to declare.

Abstract 4136 Objective To investigate the frequency of nucleophosmin(NPM1) gene mutations and FLT3 mutations in Chinese patients with acute myeloid leukemia (AML) and its correlation with clinical feature and prognosis. Methods 123 first diagnosed AML patients were involved in our study. Polymerase chain reaction (PCR) combined with electrophoresis was directly used to detect FLT3-ITD mutations, PCR combined with EcoRV digestion was used to detect FLT3-TKD mutation, and PCR combined with directly sequencing was used to detect NPM1 mutations. Results (1) In the 123 first diagnosed AML patients, 16 patients (13.0%) were found harboring FLT3-ITD mutation, 6 patients (4.9%) were FLT3-TKD positive, and one patient was found harboring co-existing FLT3-ITD and FLT3-TKD mutation. In addition, 24 patients (19.8%) were NPM1 positive, including 22 patients with A-type mutation, one patient with B-type mutation and one patient with D-type mutation. 5 patients were found harboring co-existing FLT3-ITD and NPM1 mutation. (2) FLT3-ITD and NPM1 mutations were identified as 17.5% (10/57) and 31.6% (18/57) individually in 57 AML patients with normal karyotype, which were significantly higher than patients with abnormal karyotype. All of patients with double mutation had normal karyotype. (3) White blood cell (WBC) count and leukemia cell of bone marrow in FLT3-ITD or FLT3-ITD+/NPM1+ patients were both higher than those patients with FLT3-ITD-/NPM1-. The CR rate of FLT3-ITD+/NPM1-, FLT3-ITD+/NPM1+, FLT3-ITD-/NPM1+, FLT3-ITD-/NPM1- were 50% (4/8), 20% (1/5), 87.5% (7/8), 79.5% (35/44) individually. Conclusions FLT3 gene and NPM1 gene mutations are common in AML patients, and early detection of FLT3 gene and NPM1 gene mutations will be beneficial for treatment and prognosis analysis of AML patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 4990 Recently there were two different model about clone genesis of acute myeloid leukemia (AML) transformed from pre-existing JAK2 V617F positive myeloproliferative neoplasm (MPN). One model showed the leukemia cells were come from JAK2 V617F negative clone, however, the other indicated that the leukemia cells were still developed from JAK2 V617F positive clone. Here, we report a elderly AML patient who was developed from pre-existing myelofibrosis (MF) with homozygous JAK2 V617F mutation. In leuekmic transformation phase, heterozygous JAK2 V617F mutation was identified, supported the idea that the leukemia cells may be come from JAK2 V617F negative clone. Moreover, no other cytogenetic and molecular genetic abnormalities were further found. After one course of CAG regimen, complete remission was achieved. Further follow-up is still in progress. Disclosures No relevant conflicts of interest to declare.

In recent three years the new notable progress associated with myeloproliferative disorder (MPD) was the identification of JAK2 and MPL mutations, which have been confirmed to be the major molecular mechanism and marker of BCR/ABL negative MPD. Multiple techniques including allele-specific PCR, conventional DNA sequencing, pyrosequencing as well as BsaXI restriction analysis have been used to detect these mutations. The previous data of Shanghai Group had demonstrated the sensitivity and preliminary result of JAK2 V617F in 162 Chinese patients with MPD using MassARRAY assay. To generally identify the frequency of these mutations in Chinese MPD patients, we continued to employ this technique-MassARRAY assay to detect JAK2 V617F, JAK2 K539L as well as MPL W515L mutation in a larger scale of Chinese MPD patients. A total of 204 Chinese MPD patients were enrolled in our study. These patients were referred to polycythemia vera (PV) (n=55), essential thrombocythemia (ET) (n=110), primary myelofibrosis (PMF) (n=29) and hypereosinophilic syndrome (HES) (n=10). 2 ml peripheral blood was obtained with informed consent and genomic DNA was isolated. The diagnosis of MPD was established according to the 2001 WHO diagnostic criteria. Finally, 187 patient samples with good signal can be analyzed for JAK2 V617F mutation. Among the available 101 signals of ET patients, 30 were heterozygous mutation and 9 were homozygous mutation. Among 52 PV patients, 25 were heterozygous mutation and 14 were homozygous mutation. Among 25 PMF patients, 9 were heterozygous mutation and 5 were homozygous mutation. None of HES patients was found harboring JAK2 V617F. In addition, we identified a PV patient harboring JAK2 K539L but not V617F mutation (1/52, 1.9%), and an ET patient harboring MPL W515L mutation (1/101, 1%). Both results were further confirmed by sequence analysis. Hence, we concluded that JAK2 V617F underlie the major molecular pathogenesis of Chinese MPD patients especially PV, however, JAK2 K539L and MPL W515L are rare events in these patients.

Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell disease with distinct biology and clinical features. According to clinical and biology process, CML can be divided as two different phase: the initial chronic phase (CP) and progression phase including accelerated phase (AP) followed by blast crisis (BC). In a previous study, we have identified the transcription factor GATA-2 L359V mutation in CML BC patients but not CP and its pivotal role in CML progression (PNAS 2008 105:2076–2081). Here, we continued to explore the occurrence of GATA-2 L359V mutation in other hematological malignancies using Mass-ARRAY assay and sequence analysis. A total of 652 patient samples were included in our study. These patients were referred to 270 Acute Myeloid Leukemia (AML) including M1–M7, 30 Myelodysplastic Syndrome (MDS), 50 Acute Lymphoblastic Leukemia (ALL), 12 Chronic Lymphocytic Leukemia (CLL), 40 CML CP and 250 BCR/ABL negative Myeloproliferative Disorder (MPD) patients. 5 ml bone marrow sample before therapy was collected with informed consent and genomic DNA was isolated. The diagnosis of AML, ALL, CML, CLL, MDS and MPD was established according to the 2001 WHO diagnostic criteria. In addition, 8 samples of CML BC harboring GATA-2 L359V were supplied into our study as positive control and 100 peripheral blood samples of healthy adult as normal control. As a result, no L359V mutation was detected in AML, ALL, MDS, CLL, BCR/ABL negative MPD and CML CP. Our data strongly suggested that GATA-2 L359V is solely associated with CML progression but not other hematological malignancies. Therefore, we favored this idea, i.e., BCR/ABL underlies the pathogenic basis of CML CP; However, subsequent genomic instabilities contribute to mutation of key transcription factor such as GATA-2 which ultimately trigger the blastic transformation of CML.

Acquisition of additional genetic and/or epigenetic abnormalities other than BCR/ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast phase. To gain insights into the underlying mechanisms, we screened DNA samples from CML patients during acute transformation for alterations in a number of transcription factor genes crucial to myeloid-lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of GATA-2, a negative regulator of hematopoietic stem/progenitor cell differentiation. L359V within zinc finger domain (ZF) 2 of GATA-2 was found in 8 cases with myelo-monoblastic features, while an in-frame deletion of six amino acids (D341–346) across the border of ZF1 was detected in 1 patient at blast crisis with eosinophilia. Further studies showed that L359V not only increased transactivation activity, but also enhanced inhibitory effects on the major myelopoietic regulator PU.1. Consistent with the myelo-monoblastic features of CML patients with GATA-2 L359V mutant, transduction of GATA-2 L359V mutant into HL-60 cells or BCR/ABL-harboring mouse model disturbed myelo-monocytic differentiation/proliferation in vitro and in vivo, respectively. These data suggest that GATA-2 mutations may be involved in acute myeloid transformation in some CML patients.

Objectives To evaluate the prevalence and association with clinical features of FLT3 internal tandem duplication (FLT3-ITD) in patients with newly-diagnosed acute promyelocytic leukemia (APL). Methods A total of 103 APL patients were screened by polymerase chain reaction (PCR) for FLT3-ITD. Results FLT3-ITD mutations were identified in 19.4% (20/103) patients. The FLT3-ITD was associated with short/variant form of PML-RARα isoforms (p Conclusion FLT3-ITDs were frequently identified in patients with newly diagnosed APL. FLT3-ITD was associated with short/variant form of PML-RARα fusion gene and increased initial WBC. No significant impact of FLT3-ITD on treatment outcome was observed with limited follow-up. Association of FLT3-ITD and PML-RARα isoforms in patients with APL No FLT3-ITD+ FLT3-ITD− Long 57 2(3.5%) 55(96.5%) Short 41 16(39.0%) 25(61.0%) Variant 5 2(40%) 3(60%) Total 103 20(19.4%) 83(80.6%) FLT3 expression in different patient sample FLT3 expression in different patient sample FLT3 expression in different patient sample FLT3 expression in different patient sample