Chronic Myeloid Leukemia in Lymphoid Blast Crisis Post-Complete Remission Transforming to Therapy-Related Acute Myeloid Leukemia: A Case Report and Literature Review

Chronic Myeloid Leukemia in Lymphoid Blast Crisis Post-Complete Remission Transforming to Therapy-Related Acute Myeloid Leukemia: A Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Chronic Myeloid Leukemia in Lymphoid Blast Crisis Post-Complete Remission Transforming to Therapy-Related Acute Myeloid Leukemia: A Case Report and Literature Review Lulu Li, Shumei Bai, Xuxiao Guo, Xin ling, Zhaoxia Liu, Yaqin Luo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7273025/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract We retrospectively analyzed a case of therapy-related acute myeloid leukemia (t-AML) developing after complete remission of chronic myeloid leukemia in lymphoid blast crisis (CML-LBC), admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine in March 2020. A 48-year-old female was initially diagnosed with chronic myeloid leukemia (P210-positive) at a local hospital in 2018 and received dasatinib targeted therapy. In March 2020, she was admitted to our institution with transformed lymphoid blast crisis. Genetic analysis revealed a homozygous F317L mutation in the ABL1 kinase domain of the BCR/ABL fusion gene, prompting a switch to nilotinib targeted therapy. In February 2024, bone marrow morphology showed 15% myeloid blasts. Comprehensive diagnostic evaluation integrating morphological assessment, immunophenotyping, and molecular genetics confirmed the diagnosis: transformation of chronic myeloid leukemia to therapy-related acute myeloid leukemia. Chronic Myeloid Leukemia Lymphoid Blast Crisis Therapy-Related Acute Myeloid Leukemia Tyrosine Kinase Inhibitors Clonal Evolution Figures Figure 1 Figure 2 Background Chronic myeloid leukemia (CML) is a malignant clonal proliferative disorder originating from hematopoietic stem cells, characterized by the t(9;22)(q34;q11) chromosomal translocation. Its natural course historically comprised three phases: chronic phase (CP), accelerated phase (AP), and blast crisis (BC). Notably, the 2022 WHO Classification of Hematolymphoid Tumors (5th edition) has eliminated the AP as a distinct category; however, a subset of patients still progress through a high-risk transitional stage with imminent risk of transformation to BC[1, 2]. CML-BC represents the terminal disease phase, and once patients progress to blast crisis, prognosis becomes dismal. CML blast crisis may evolve into various acute leukemia subtypes, including myeloid, lymphoid, or bilineage phenotypes[3]. There have been no reports in the literature of CML progressing to lymphoid blast cri-sis, achieving complete remission (CR), and subsequently developing t-AML. We herein retrospectively analyze the clinical features and management of a patient with CML in lymphoid blast crisis who achieved CR and subsequently developed t-AML, supplemented by a comprehensive literature review. This case aims to enhance clinical insights into the diagnosis and treatment of this uncommon disease trajectory. Case Report A 48-year-old female presented with unexplained abdominal distension in February 2018. Initial evaluation at a local hospital revealed complete blood count ab-normalities including leukocytosis (WBC 489.28×10⁹/L), neutrophilia (442.03×10⁹/L), basophilia (11.44×10⁹/L), hemoglobin 99 g/L, and platelets 112×10⁹/L. Cytogenetic analysis identified the Philadelphia chromosome with karyotype 46,XX,t(9;22)(q34;q11.2) . Molecular testing confirmed BCR-ABL1 P210 fusion gene positivity (130.83% IS). These findings established the diagnosis of chronic myeloid leukemia (P210-positive), and she began targeted therapy with dasatinib 50–100 mg once daily. In March 2020, the patient was admitted to our institution following disease progression to lymphoid blast crisis. Peripheral blood examination demonstrated WBC 84.02×10⁹/L, HGB 128 g/L, PLT 14×10⁹/L with 43% blasts. Bone marrow aspiration revealed hypercellular marrow infiltrated by 71% lymphoblasts (Fig. 1 A). Flow cytometric analysis detected an aberrant immunophenotypic population comprising 80.5% of nucleated cells, expressing HLA-DR, CD10, CD19, CD22, CD34, TdT with partial CD13 and CD38 positivity. BCR-ABL1 P210 transcript levels had risen to 270.25% IS. The collective evidence confirmed transformation to chronic myeloid leukemia in lymphoid blast crisis (BCR-ABL1 P210-positive). She received sequential chemotherapy regimens: initial VD protocol (vindesine/dexamethasone) with dasatinib followed by intensified VDCP therapy (vindesine/doxorubicin/cyclophosphamide/prednisone) with dasatinib. By June 2021, persistent bone marrow hypercellularity was observed (Fig. 1 B). Minimal residual disease assessment indicated refractory or relapsed B-ALL (Fig. 2 A). Sanger sequencing subsequently identified a homozygous F317L mutation within the ABL1 ki-nase domain, prompting therapeutic transition to nilotinib 400 mg twice daily. Be-tween July 2021 and June 2022, she underwent additional chemotherapy cycles including VD, VICP (vindesine/idarubicin/cyclophosphamide/pegaspargase), and COEP (cyclophosphamide/vincristine/etoposide/prednisone). October 2023 reassessment confirmed complete remission status: bone marrow morphology showed scattered lymphoblasts (Fig. 1 C), BCR-ABL1 P210 transcripts declined to 0.032% IS, and flow cytometric MRD levels were below 10⁻⁴ (Fig. 2 B). She continued maintenance nilotinib 400 mg twice daily as outpatient therapy.. In February 2024, hematologic transformation to t-AML occurred. Bone marrow examination revealed hypercellularity with 15% blasts (Fig. 1 D) exhibiting partial myeloperoxidase (POX) positivity (Fig. 1 E). Flow cytometry identified 26.14% monoblastic cells characterized by CD64⁺CD14ᵈⁱᵐ/⁻CD300e⁻HLA-DRᵈⁱᵐ/⁻ immunopheno-type (Fig. 2 C). BCR-ABL1 was undetectable. Comprehensive diagnostic evaluation confirmed transformation to t-AML. From March through July 2024, she received combination therapy with HAG regimen (homoharringtonine/cytarabine/G-CSF), EA protocol (etoposide/cytarabine), nilotinib and venetoclax. Treatment courses were complicated by recurrent neutropenia-associated infections requiring broad-spectrum antibiotics including meropenem and tigecycline. August 2024 evaluation demonstrated hypocellular bone marrow containing 4% lymphoblasts and 2% monoblasts. Flow cytometry detected 27.83% immature myeloid cells with an abnormal T-lymphocyte CD4⁺/CD8⁺ ratio. Peripheral blood analysis confirmed BCR-ABL1 negativity (P190/P210 negative, BCR-ABL1/ABL1 0). The patient continues nilotinib 400 mg twice daily with scheduled minimal residual disease surveillance. Discussion CML represents a hematologic malignancy characterized by the Philadelphia chromosome (Ph), with constitutive activation of the BCR-ABL tyrosine kinase serving as the core oncogenic driver. This aberrant kinase activity promotes granulocyte hyperproliferation through dysregulation of downstream signaling pathways[4]. We present a rare and clinically complex CML case featuring initial progression from chronic phase to LBC, followed by transformation to t-AML after CR. This dual trans-formation trajectory implicates multifaceted mechanisms including disease biological heterogeneity, therapy-driven clonal evolution, and hematopoietic stem cell (HSC) plasticity, posing significant diagnostic and therapeutic challenges. The development of lymphoid blast crisis in CML is intrinsically linked to pathological BCR-ABL1 kinase activity. Through constitutive activation of diverse intra-cellular signaling cascades, BCR-ABL1 induces uncontrolled hematopoietic stem cell proliferation and accumulation of genetic aberrations, ultimately leading to lymphoid or myeloid differentiation arrest[5]. In our patient, the markedly elevated baseline BCR-ABL1 P210 transcript level (130.83% IS) at initial diagnosis suggested high tumor burden potentially accelerating clonal heterogeneity. Notably, subsequent detection of the F317I mutation within the ABL1 kinase domain during lymphoid blast crisis “a known dasatinib resistance mutation retaining partial sensitivity to nilotinib[6]”. correlates with her achievement of CR following tyrosine kinase inhibitor (TKI) switch. The transformation to t-AML post-CR involves more intricate mechanisms. Primarily, prolonged exposure to cytotoxic agents, including alkylators (e.g., cyclo-phosphamide) and topoisomerase II inhibitors (e.g., etoposide), can drive clonal evolution through DNA damage induction and epigenetic alterations, culminating in therapy-related myeloid neoplasms [7, 8]. Our patient's treatment history with multiple chemotherapeutic regimens (VDCP, VICP) establishes cumulative exposure consistent with classical t-AML triggers. Secondly, flow cytometry detection of CD64⁺CD14ᵈⁱᵐ/⁻ monoblastic cells with concomitant BCR-ABL1 negativity suggests t-AML likely originated from a novel therapy related clone rather than reactivation of the original Ph⁺ clone. This observation aligns with clonal evolution theory wherein therapeutic pressure promotes selection of aggressive subclones with survival advantages [9]. Critical diagnostic considerations include distinguishing t-AML from CML myeloid blast crisis or de novo AML. The absence of BCR::ABL1 combined with characteristic immunophenotype (HLA-DR⁻/CD300e⁻) effectively excludes CML blast crisis. Genomically, t-AML frequently harbors high-risk aberrations such as TP53 mutations[10], whereas CML blast crisis typically demonstrates RUNX1 or IKZF1 abnormalities[11]. The lack of canonical CML blast crisis-associated mutations in our case, alongside documented chemotherapeutic exposure, further supports t-AML diagnosis. Com-pared to de novo AML, t-AML portends dismal prognosis due to adverse genetic pro-files, advanced age, and comorbidities[12]. This case underscores the complexity of clonal dynamics post-CML blast crisis and the potential leukemogenic risk of chemotherapeutic agents. For CML patients receiving long-term TKI and intensive chemotherapy, dynamic monitoring of minimal residual disease (MRD) and clonal evolution remains imperative[13]. Future investigations warrant comprehensive genomic profiling via whole-exome sequencing to delineate secondary mutation spectra and guide targeted therapeutic strategies. Declarations Acknowledgments This study was funded by the Shandong Science and Technology Development Program for Medical and Health (No.202203040256). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval and consent to participate Informed written consent was obtained from the patient for publication of his case along with pathology images. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare no competing interests. References KHOURY J D, SOLARY E, ABLA O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia, 2022 ; 36(7): 1703-19. SHANMUGANATHAN N, HUGHES T P. Accelerated-phase CML: de novo and transformed. Hematology American Society of Hematology Education Program, 2023 ; 2023(1): 459-68. COPLAND M. Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity. Br J Haematol, 2022 ; 199(5): 665-78. JABBOUR E, KANTARJIAN H. Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring. 2024 ; 99(11): 2191-212. SAVONA M, TALPAZ M. Getting to the stem of chronic myeloid leukaemia. Nature Reviews Cancer, 2008 ; 8(5): 341-50. JABBOUR E, KANTARJIAN H M, JONES D, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood, 2008 ; 112(13): 4839-42. VENUGOPAL S, DEZERN A E. Therapy-related myelodysplastic syndromes and acute myeloid leukemia. Seminars in Hematology, 2024 ; 61(6): 379-84. BOLTON K L, PTASHKIN R N, GAO T, et al. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nature genetics, 2020 ; 52(11): 1219-26. FABIANI E, CRISTIANO A, HAJRULLAJ H, et al. Therapy-Related Myeloid Neoplasms: Predisposition and Clonal Evolution. Mediterranean journal of hematology and infectious diseases, 2023 ; 15(1): e2023064. WONG T N, RAMSINGH G, YOUNG A L, et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature, 2015 ; 518(7540): 552-5. ADNAN AWAD S, DUFVA O, IANEVSKI A, et al. RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses. Leukemia, 2021 ; 35(4): 1087-99. GROSS S, IHLOW J, BUSACK L, et al. Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy. Blood cancer journal, 2024 ; 14(1): 160. GANSER A, HEUSER M. Therapy-related myeloid neoplasms. 2017 ; 24(2): 152-8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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figure legend\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7273025/v1/6638ca1f4e5091fd0686facd.png"},{"id":92509900,"identity":"65d58681-e035-485c-bbb3-a401e2711f3a","added_by":"auto","created_at":"2025-09-30 13:17:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":38516654,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7273025/v1/6f705efe-e58e-414f-ae92-857803f5072e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eChronic Myeloid Leukemia in Lymphoid Blast Crisis Post-Complete Remission Transforming to Therapy-Related Acute Myeloid Leukemia: A Case Report and Literature Review\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eChronic myeloid leukemia (CML) is a malignant clonal proliferative disorder originating from hematopoietic stem cells, characterized by the \u003cem\u003et(9;22)(q34;q11)\u003c/em\u003e chromosomal translocation. Its natural course historically comprised three phases: chronic phase (CP), accelerated phase (AP), and blast crisis (BC). Notably, the 2022 WHO Classification of Hematolymphoid Tumors (5th edition) has eliminated the AP as a distinct category; however, a subset of patients still progress through a high-risk transitional stage with imminent risk of transformation to BC[1, 2]. CML-BC represents the terminal disease phase, and once patients progress to blast crisis, prognosis becomes dismal. CML blast crisis may evolve into various acute leukemia subtypes, including myeloid, lymphoid, or bilineage phenotypes[3]. There have been no reports in the literature of CML progressing to lymphoid blast cri-sis, achieving complete remission (CR), and subsequently developing t-AML. We herein retrospectively analyze the clinical features and management of a patient with CML in lymphoid blast crisis who achieved CR and subsequently developed t-AML, supplemented by a comprehensive literature review. This case aims to enhance clinical insights into the diagnosis and treatment of this uncommon disease trajectory.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 48-year-old female presented with unexplained abdominal distension in February 2018. Initial evaluation at a local hospital revealed complete blood count ab-normalities including leukocytosis (WBC 489.28×10⁹/L), neutrophilia (442.03×10⁹/L), basophilia (11.44×10⁹/L), hemoglobin 99 g/L, and platelets 112×10⁹/L. Cytogenetic analysis identified the Philadelphia chromosome with karyotype \u003cem\u003e46,XX,t(9;22)(q34;q11.2)\u003c/em\u003e. Molecular testing confirmed BCR-ABL1 P210 fusion gene positivity (130.83% IS). These findings established the diagnosis of chronic myeloid leukemia (P210-positive), and she began targeted therapy with dasatinib 50–100 mg once daily.\u003c/p\u003e\u003cp\u003eIn March 2020, the patient was admitted to our institution following disease progression to lymphoid blast crisis. Peripheral blood examination demonstrated WBC 84.02×10⁹/L, HGB 128 g/L, PLT 14×10⁹/L with 43% blasts. Bone marrow aspiration revealed hypercellular marrow infiltrated by 71% lymphoblasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Flow cytometric analysis detected an aberrant immunophenotypic population comprising 80.5% of nucleated cells, expressing HLA-DR, CD10, CD19, CD22, CD34, TdT with partial CD13 and CD38 positivity. BCR-ABL1 P210 transcript levels had risen to 270.25% IS. The collective evidence confirmed transformation to chronic myeloid leukemia in lymphoid blast crisis (BCR-ABL1 P210-positive). She received sequential chemotherapy regimens: initial VD protocol (vindesine/dexamethasone) with dasatinib followed by intensified VDCP therapy (vindesine/doxorubicin/cyclophosphamide/prednisone) with dasatinib. By June 2021, persistent bone marrow hypercellularity was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Minimal residual disease assessment indicated refractory or relapsed B-ALL (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Sanger sequencing subsequently identified a homozygous F317L mutation within the ABL1 ki-nase domain, prompting therapeutic transition to nilotinib 400 mg twice daily. Be-tween July 2021 and June 2022, she underwent additional chemotherapy cycles including VD, VICP (vindesine/idarubicin/cyclophosphamide/pegaspargase), and COEP (cyclophosphamide/vincristine/etoposide/prednisone). October 2023 reassessment confirmed complete remission status: bone marrow morphology showed scattered lymphoblasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), BCR-ABL1 P210 transcripts declined to 0.032% IS, and flow cytometric MRD levels were below 10⁻⁴ (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). She continued maintenance nilotinib 400 mg twice daily as outpatient therapy..\u003c/p\u003e\u003cp\u003eIn February 2024, hematologic transformation to t-AML occurred. Bone marrow examination revealed hypercellularity with 15% blasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD) exhibiting partial myeloperoxidase (POX) positivity (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). Flow cytometry identified 26.14% monoblastic cells characterized by CD64⁺CD14ᵈⁱᵐ/⁻CD300e⁻HLA-DRᵈⁱᵐ/⁻ immunopheno-type (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). BCR-ABL1 was undetectable. Comprehensive diagnostic evaluation confirmed transformation to t-AML. From March through July 2024, she received combination therapy with HAG regimen (homoharringtonine/cytarabine/G-CSF), EA protocol (etoposide/cytarabine), nilotinib and venetoclax. Treatment courses were complicated by recurrent neutropenia-associated infections requiring broad-spectrum antibiotics including meropenem and tigecycline. August 2024 evaluation demonstrated hypocellular bone marrow containing 4% lymphoblasts and 2% monoblasts. Flow cytometry detected 27.83% immature myeloid cells with an abnormal T-lymphocyte CD4⁺/CD8⁺ ratio. Peripheral blood analysis confirmed BCR-ABL1 negativity (P190/P210 negative, BCR-ABL1/ABL1 0). The patient continues nilotinib 400 mg twice daily with scheduled minimal residual disease surveillance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCML represents a hematologic malignancy characterized by the Philadelphia chromosome (Ph), with constitutive activation of the BCR-ABL tyrosine kinase serving as the core oncogenic driver. This aberrant kinase activity promotes granulocyte hyperproliferation through dysregulation of downstream signaling pathways[4]. We present a rare and clinically complex CML case featuring initial progression from chronic phase to LBC, followed by transformation to t-AML after CR. This dual trans-formation trajectory implicates multifaceted mechanisms including disease biological heterogeneity, therapy-driven clonal evolution, and hematopoietic stem cell (HSC) plasticity, posing significant diagnostic and therapeutic challenges.\u003c/p\u003e\u003cp\u003eThe development of lymphoid blast crisis in CML is intrinsically linked to pathological BCR-ABL1 kinase activity. Through constitutive activation of diverse intra-cellular signaling cascades, BCR-ABL1 induces uncontrolled hematopoietic stem cell proliferation and accumulation of genetic aberrations, ultimately leading to lymphoid or myeloid differentiation arrest[5]. In our patient, the markedly elevated baseline BCR-ABL1 P210 transcript level (130.83% IS) at initial diagnosis suggested high tumor burden potentially accelerating clonal heterogeneity. Notably, subsequent detection of the F317I mutation within the ABL1 kinase domain during lymphoid blast crisis \u0026ldquo;a known dasatinib resistance mutation retaining partial sensitivity to nilotinib[6]\u0026rdquo;. correlates with her achievement of CR following tyrosine kinase inhibitor (TKI) switch. The transformation to t-AML post-CR involves more intricate mechanisms. Primarily, prolonged exposure to cytotoxic agents, including alkylators (e.g., cyclo-phosphamide) and topoisomerase II inhibitors (e.g., etoposide), can drive clonal evolution through DNA damage induction and epigenetic alterations, culminating in therapy-related myeloid neoplasms [7, 8]. Our patient's treatment history with multiple chemotherapeutic regimens (VDCP, VICP) establishes cumulative exposure consistent with classical t-AML triggers. Secondly, flow cytometry detection of CD64⁺CD14ᵈⁱᵐ/⁻ monoblastic cells with concomitant BCR-ABL1 negativity suggests t-AML likely originated from a novel therapy related clone rather than reactivation of the original Ph⁺ clone. This observation aligns with clonal evolution theory wherein therapeutic pressure promotes selection of aggressive subclones with survival advantages [9].\u003c/p\u003e\u003cp\u003eCritical diagnostic considerations include distinguishing t-AML from CML myeloid blast crisis or \u003cem\u003ede novo\u003c/em\u003e AML. The absence of BCR::ABL1 combined with characteristic immunophenotype (HLA-DR⁻/CD300e⁻) effectively excludes CML blast crisis. Genomically, t-AML frequently harbors high-risk aberrations such as TP53 mutations[10], whereas CML blast crisis typically demonstrates RUNX1 or IKZF1 abnormalities[11]. The lack of canonical CML blast crisis-associated mutations in our case, alongside documented chemotherapeutic exposure, further supports t-AML diagnosis. Com-pared to de novo AML, t-AML portends dismal prognosis due to adverse genetic pro-files, advanced age, and comorbidities[12]. This case underscores the complexity of clonal dynamics post-CML blast crisis and the potential leukemogenic risk of chemotherapeutic agents. For CML patients receiving long-term TKI and intensive chemotherapy, dynamic monitoring of minimal residual disease (MRD) and clonal evolution remains imperative[13]. Future investigations warrant comprehensive genomic profiling via whole-exome sequencing to delineate secondary mutation spectra and guide targeted therapeutic strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Shandong Science and Technology Development Program for Medical and Health (No.202203040256).\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eInformed written consent was obtained from the patient for publication of his case along with pathology images.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003eA copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKHOURY J D, SOLARY E, ABLA O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia, \u003cstrong\u003e2022\u003c/strong\u003e; 36(7): 1703-19.\u003c/li\u003e\n\u003cli\u003eSHANMUGANATHAN N, HUGHES T P. Accelerated-phase CML: de novo and transformed. Hematology American Society of Hematology Education Program, \u003cstrong\u003e2023\u003c/strong\u003e; 2023(1): 459-68.\u003c/li\u003e\n\u003cli\u003eCOPLAND M. Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity. Br J Haematol, \u003cstrong\u003e2022\u003c/strong\u003e; 199(5): 665-78.\u003c/li\u003e\n\u003cli\u003eJABBOUR E, KANTARJIAN H. Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring. \u003cstrong\u003e2024\u003c/strong\u003e; 99(11): 2191-212.\u003c/li\u003e\n\u003cli\u003eSAVONA M, TALPAZ M. Getting to the stem of chronic myeloid leukaemia. 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Mediterranean journal of hematology and infectious diseases, \u003cstrong\u003e2023\u003c/strong\u003e; 15(1): e2023064.\u003c/li\u003e\n\u003cli\u003eWONG T N, RAMSINGH G, YOUNG A L, et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature, \u003cstrong\u003e2015\u003c/strong\u003e; 518(7540): 552-5.\u003c/li\u003e\n\u003cli\u003eADNAN AWAD S, DUFVA O, IANEVSKI A, et al. RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses. Leukemia, \u003cstrong\u003e2021\u003c/strong\u003e; 35(4): 1087-99.\u003c/li\u003e\n\u003cli\u003eGROSS S, IHLOW J, BUSACK L, et al. Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy. Blood cancer journal, \u003cstrong\u003e2024\u003c/strong\u003e; 14(1): 160.\u003c/li\u003e\n\u003cli\u003eGANSER A, HEUSER M. Therapy-related myeloid neoplasms. \u003cstrong\u003e2017\u003c/strong\u003e; 24(2): 152-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chronic Myeloid Leukemia, Lymphoid Blast Crisis, Therapy-Related Acute Myeloid Leukemia, Tyrosine Kinase Inhibitors, Clonal Evolution","lastPublishedDoi":"10.21203/rs.3.rs-7273025/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7273025/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe retrospectively analyzed a case of therapy-related acute myeloid leukemia (t-AML) developing after complete remission of chronic myeloid leukemia in lymphoid blast crisis (CML-LBC), admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine in March 2020. A 48-year-old female was initially diagnosed with chronic myeloid leukemia (P210-positive) at a local hospital in 2018 and received dasatinib targeted therapy. In March 2020, she was admitted to our institution with transformed lymphoid blast crisis. Genetic analysis revealed a homozygous F317L mutation in the ABL1 kinase domain of the BCR/ABL fusion gene, prompting a switch to nilotinib targeted therapy. In February 2024, bone marrow morphology showed 15% myeloid blasts. Comprehensive diagnostic evaluation integrating morphological assessment, immunophenotyping, and molecular genetics confirmed the diagnosis: transformation of chronic myeloid leukemia to therapy-related acute myeloid leukemia.\u003c/p\u003e","manuscriptTitle":"Chronic Myeloid Leukemia in Lymphoid Blast Crisis Post-Complete Remission Transforming to Therapy-Related Acute Myeloid Leukemia: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 10:37:30","doi":"10.21203/rs.3.rs-7273025/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7cf6ab33-1893-46bc-a42d-d65461f0f976","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-30T13:09:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-08 10:37:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7273025","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7273025","identity":"rs-7273025","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}