Background
Inversion(16)(p13.1q22)/CBFB::MYH11 or t(16;16) acute myeloid leukemia (AML) results from a translocation between the core-binding factor (CBF) β subunit (CBFB) at 16q22 and the myosin heavy chain 11 smooth muscle gene (MYH11) at 16p13.1. The resulting CBFB::MYH11 rearrangement generates a fusion protein that alters transcriptional regulation in hematopoiesis, leading to maturation arrest and leukemic transformation, often in conjunction with mutations affecting the mitogen-activated protein kinase pathway.1–3 These leukemias account for 12% to 15% of all AML cases and typically respond favorably to cytarabine-based therapeutic regimens, achieving high remission rates and long-term disease-free and overall survival (OS).4–6
Morphologically, inversion(16) [inv(16)] AML typically presents with a prominent monocytic component, eosinophilia, and abnormalities involving eosinophilic granules during the late promyelocyte and myelocyte stages of eosinophil maturation.7 Occasionally, patients with CBFB::MYH11 may not manifest these morphologic features and can present as a myelodysplastic neoplasm/syndrome (MDS) with <20% blasts.8 The presence of CBFB::MYH11 in patients with myeloid neoplasms is considered an AML-defining abnormality by both the WHO and International Consensus Classification (ICC) systems.9,10 Importantly, in the European LeukemiaNet (ELN) risk classification,11 inv(16) AML is classified as a favorable-risk abnormality associated with a superior prognosis.12,13 The frontline FLAG-GO regimen (fludarabine, cytarabine, granulocyte colony-stimulating factor, and low-dose gemtuzumab ozogamicin) achieves a 95% complete remission rate, with 3-year relapse-free survival and OS rates of 85% and 78%, respectively.13 In contrast, other AML subtypes historically have a dismal prognosis when treated with high-intensity chemotherapy, with a 5-year relapse-free survival between 15% and 32% before the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and novel therapies.14 Given its favorable prognosis, allo-HSCT is generally not recommended for patients with inv(16)/CBFB::MYH11 AML who achieve a first complete remission, except for those with persistent minimal (measurable) residual disease (MRD).15,16 Due to the significant diagnostic, prognostic, and therapeutic implications of CBFB::MYH11, accurate and timely detection is essential for optimizing AML management with curative intent.
Identification of inv(16) or t(16;16) is routinely performed using conventional G-banding (CG) karyotyping, followed by confirmation with fluorescence in situ hybridization (FISH) and/or reverse-transcriptase PCR (RT-PCR).10 However, because the pericentric inversion of chromosome 16 can be subtle, CG may miss the abnormality in up to one-third of patients.17 Furthermore, CG has limited resolution for detecting alterations <10 megabase (Mb) and often yields no or insufficient metaphases (<20) for optimal interpretation in 27% of cases due to its reliance on cell culture.17–20 Confirmatory FISH and/or RT-PCR are targeted assays designed to detect for specific genes or regions of interest and are typically performed when CG or morphologic findings raise suspicion.21,22 Because CBFB::MYH11 can have multiple translocation breakpoints, RT-PCR requires multiple primer combinations to identify most alternative transcripts. RT-PCR has the highest sensitivity that permits baseline confirmation and subsequent detection of MRD for therapy response assessment.23 Therefore, a combination of these techniques is used in clinical laboratories for CBFB::MYH11 detection.
In this scenario, an unbiased, genome-wide assay would be helpful for the accurate and timely detection of actionable alterations. Optical genome mapping (OGM) has emerged as a novel, clinically feasible technique capable of genome-wide detection of all types of chromosomal structural variants at a high resolution at the gene and/or exon level.24 In this case report, we present a patient who was diagnosed with therapy-related MDS (t-MDS) following cytotoxic therapy, with trisomy 8 abnormality, and treated with low-dose decitabine. Subsequently, the patient was found to have inv(16)/CBFB::MYH11 rearrangement by CG and FISH, compatible with transformation to AML, but tested negative for the rearrangement by RT-PCR. Out of interest, retrospective OGM analysis was performed on samples from both the initial MDS diagnosis and subsequent AML transformation. CBFB::MYH11 was detected at both time points, highlighting the potential implications of earlier detection on treatment decisions and prognosis. Furthermore, OGM enabled the comprehensive characterization of a novel CBFB::MYH11 transcript with noncanonical breakpoints, undetectable by current standard-of-care assays, revealing a critical diagnostic blind spot in current methodologies.
Case Report
Initial Presentation and Diagnosis of Therapy-Related MDS
A 43-year-old woman presented to her local oncologist with worsening pancytopenia, with a WBC count of 1.8 × 109/L, absolute neutrophil count of 0.51 × 109/L, hemoglobin level of 10.4 g/dL, and platelet count of 47 × 109/L. Her medical history included Burkitt-like aggressive B-cell lymphoma diagnosed 10 months prior, treated with 8 cycles of R-EPOCH (rituximab/etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin), with end-of-treatment PET/CT showing a complete metabolic response. Repeat lactate dehydrogenase testing showed an elevated level of 284 U/L (upper limit of normal, 214 U/L), raising concern for relapsed lymphoma. PET/CT revealed an avid submandibular node, reportedly negative for lymphoma or carcinoma based on ultrasound-guided biopsy. Due to developing pancytopenia, a bone marrow (BM) biopsy was performed, showing 40% cellularity with 11% blasts. The patient was started locally on dexamethasone at 16 mg/day.
An in-house repeat BM aspiration and biopsy at our institution demonstrated variably cellular (20%–50%) BM with multilineage dysplasia, 3% blasts, and no ring sideroblasts. CG identified low-level trisomy 8: 47,XX,+8[1]/46,XX[19] (Figure 1A), confirmed by FISH (3.6%). Flow cytometry detected 2.3% aberrant myeloblasts (CD45dim, CD34inc, CD117inc, CD13+, CD19+, CD33+, CD64partial, CD123+, CD38+). Next-generation sequencing using an 81-gene panel revealed BRINP3 and GNAS mutations. The patient was diagnosed with t-MDS, IPSS-R low risk (score, 2.5),25 and was started on low-dose decitabine.
(A) Conventional karyotyping at baseline showing trisomy 8 in a single metaphase without inv(16). (B) Conventional karyotyping at relapse showing inv(16), confirmed by FISH using a (C) dual-color breakapart probe (Vysis, Abbott Molecular) and (D) dual-color dual-fusion CBFB::MYH11 probe (Cytocell, Oxford Gene Technology). (E) CBFB::MYH11 rearrangement detected by OGM on the Circos plot at relapse. (F, G) CBFB::MYH11 was also present at a lower variant allele frequency at diagnosis, visualized by (F) Circos plot and (G) molecule-level data.
Abbreviations: Chr, chromosome; FISH, fluorescence in situ hybridization; inv(16), inversion(16); OGM, optical genome mapping.
Citation: Journal of the National Comprehensive Cancer Network 2025; 10.6004/jnccn.2025.7015
Diagnosis of CBF AML
After 8 cycles of oral decitabine, the patient had prolonged pancytopenia, and a repeat BM biopsy showed 11% blasts. A repeat 81-gene next-generation sequencing panel showed clonal evolution with BRINP3, GNAS, and SRSF2 mutations. Unexpectedly, CG identified 46,XX,inv(16)(p13.1q22)[10]/46,XX[10] (Figure 1B). The previously detected low-level trisomy 8 was no longer observed, suggesting that inv(16) was in a different clone. FISH studies confirmed the findings using a CBFB dual-color breakapart probe (Vysis, Abbott Molecular): nuc ish(CBFBx2)(5′CBFB sep 3′CBFBx1)[134/200] in 65.5% of cultured cells from both the BM aspirate and the direct aspirate smear (Figure 1C). Results were confirmed using a dual-color, dual-fusion FISH CBFB::MYH11 probe (CytoCell, Oxford Gene Technology) (Figure 1D). Interestingly, our in-house multiplex leukemia translocation panel—an RNA-based assay that screens for most WHO-defined translocations in AML and acute lymphoblastic leukemia, including CBFB::MYH11 transcript types A, D, and E—was negative for fusions. Additionally, our in-house RT-PCR assay, designed specifically to detect CBFB::MYH11 transcript type A, was also negative, indicating the presence of alternate breakpoints affecting the fusion.
Based on this significant finding, the patient was considered to have AML transformation with acquired CBFB::MYH11 and was treated with FLAG-GO induction. A follow-up posttherapy BM aspiration and biopsy showed 6% blasts with persistent dysplastic changes and no aberrant myeloblasts on flow cytometry, a diploid karyotype by conventional karyotyping, and no detectable CBFB::MYH11 rearrangement by FISH. In-house RT-PCR was performed as part of a routine clinical order set, even though the assay failed to detect CBFB::MYH11 when inv(16) was first identified by CG before induction therapy; therefore, the negative result was not informative for MRD. The patient was started on cycle 2 of FLAG-GO.
Follow-Up
The patient was lost to follow-up at our institution after discharge from the second induction, and subsequently received a third cycle of FLAG-GO at an outside hospital. A repeat BM biopsy showed normocellular marrow with trilineage hematopoiesis, no overt dysplasia, and no detectable CBFB::MYH11 rearrangement, consistent with remission. The patient then began treatment with azacitidine and venetoclax before undergoing allo-HSCT >24 months after the initial diagnosis. The patient remains alive and in remission at 3 years posttransplant.
OGM Testing
Given that OGM provides genome-wide information on chromosomal structural variants in an objective and unbiased manner, we were interested in investigating this case using OGM as a proof-of-concept for the detection of actionable genomic aberrations that are cryptic by standard-of-care testing such as CG and RT-PCR. OGM revealed intrachromosomal translocation in chromosome 16 (Figure 1E) that mapped to CBFB::MYH11 involving intron 5 of CBFB (breakpoint GRCh38, 67,086,907) and intron 41 of MYH11 (GRCh38, 15,709,256) with a variant allele frequency (VAF) of 26%. We also performed OGM on the cryopreserved BM mononuclear cells from the initial BM sample taken at the time of initial diagnosis. Results showed an intrachromosomal translocation in chromosome 16 involving the same breakpoints that mapped to CBFB::MYH11 (VAF, ∼9%), confirming the presence of CBFB-rearranged AML at the time of initial diagnosis (Figure 1F, G). This result was also confirmed by FISH testing. OGM testing on both samples followed standard methodology as described elsewhere,26 utilizing the rare variant pipeline. The median effective coverage was 366× and 388×, respectively. Further details are provided in Supplementary Table S1, available in the supplementary materials.
We performed a retrospective review of the karyotype images from the initial diagnosis and compared them with those taken at the time of transformation. Although the banding resolution was similar at both time points, the inv(16) abnormality was not detected at the initial diagnosis, likely due to the small clone size, as indicated by the low VAF (∼9%) observed by OGM.
Discussion
Precision medicine is essential for achieving optimal outcomes in AML.27,28 This case study highlights the potential impact of genome-wide technologies for the accurate and timely detection of clinically actionable chromosomal aberrations. Several unusual features are evident in this case, such as the diagnosis of t-MDS in a young patient within a year of receiving cytotoxic therapy, including a topoisomerase II inhibitor, when the most common mean latency period is approximately 3 years.29 Additionally, the BM lacked the typical morphologic changes associated with inv(16), such as a significant increase in blasts with myelomonocytic differentiation associated with abnormal eosinophils, although these morphologic changes are known to be subtle or absent in therapy-related cases.8 Lastly, the lack of typical somatic mutations seen in MDS/AML raises the suspicion for an occult driver genetic alteration.11,28 To complicate this, CG studies at the time of initial diagnosis failed to detect the inv(16) abnormality.17,19 Furthermore, for the reasons mentioned, FISH and RT-PCR studies were not conducted at that time. At the time of AML transformation, the specific CBFB::MYH11 transcript variant was not detectable by our in-house RT-PCR (designed for the common CBFB::MYH11 transcript type A) or by the multiplex leukemia translocation screen (designed for the common CBFB::MYH11 transcript types A, D, and E), indicating that it may be a rare transcript variant.30
According to the ICC9 and WHO,10 the detection of the CBFB::MYH11 fusion is an AML-defining abnormality, and its identification would have changed the original diagnosis from t-MDS to AML with CBFB::MYH11. The case highlights a missed opportunity to offer effective frontline therapy to a patient with potentially curable CBF AML that was not recognized at the time of diagnosis. Inv(16) AML is seen in therapy-related settings in <10% of cases.31 Despite its post-cytotoxic therapy context, AML with inv(16) has a favorable risk.16 If diagnosed correctly as inv(16) AML, this patient would have initially received a cytarabine-based regimen with GO, instead of a hypomethylating agent, resulting in up to 20.7% improved survival at a 6-year follow-up.32–34 However, as emphasized in this case, despite the favorable prognostic value of inv(16), in the relapsed-disease setting, the recommendation is to pursue consolidation with allo-HSCT for patients who are candidates.16 Although allo-HSCT can offer a potential cure, it comes with the risk of inherent comorbidities, mortality, psychosocial issues, and financial toxicity, all of which could have been avoided with timely recognition of CBFB-rearranged AML.35–37 This case illustrates the importance of prompt identification of genetic and molecular alterations that impact therapeutic decisions in practice. Hence, there is a recent influx of multiple genome-wide technologies for the assessment of cytogenomic aberrations, which include both sequencing-based techniques, such as whole-genome38 and long-read39 sequencing, and non–sequencing-based techniques such as OGM, as demonstrated in this study.
OGM is a high-resolution genome mapping platform that accurately identifies structural chromosomal variants at the gene and exon level. It uses nanochannel electrophoresis to serially image fluorescently tagged ultra-high-molecular-weight DNA molecules, generating a consensus genome map from the processed images.40,41 Studies show that OGM can refine CG results in nearly 67% of cases due to its significantly higher resolution (100× to 20,000×, depending on the type of structural abnormality).42,43 OGM has demonstrated superior diagnostic accuracy and high concordance with standard-of-care techniques (CG, FISH, RT-PCR) in MDS, AML, and various hematologic malignancies, often uncovering previously unrecognized genomic complexity and achieving 100% concordance in some studies.26,42–45 Importantly, the higher resolution of OGM allows precise delineation of gene disruptions, providing accurate breakpoints at the exon level. This capability enables the identification of rarer translocations with variant breakpoints, and better characterization of genomic architecture, as illustrated in this specific case. Based on the resolution of OGM (DNA-based), the current patient shows a rearrangement between intron 5 of CBFB (67,086,907) and intron 41 of MYH11 (15,709,256), which, to our knowledge, has not been described in the literature. The most frequent CBFB::MYH11 transcript is type A (exon 5 of CBFB with exon 33 MYH11; E5::E33), which accounts for approximately 85% of all transcripts, followed by transcripts D and E, each seen in 5% of cases. Rare transcript types B, C, and F through I have only been described in single-case reports. Our in-house RT-PCR (RNA-based) uses primers targeting only the CBFB::MYH11 transcript type A, whereas our in-house leukemia translocation panel assay (also RNA-based) is designed to detect types A, D, and E. Consequently, our molecular test results were negative, highlighting the diagnostic blind spot in our current standard methodologies for detecting important actionable genetic aberrations. This finding represents a discovery of a novel, noncanonical CBFB::MYH11 transcript that, to our knowledge, has not been described in the literature. It further underscores the need for genome-wide diagnostic approaches to optimize treatment strategies.
In our previous study exploring the utility of OGM in a large series of patients with newly diagnosed MDS, numerous clinically significant structural variants that were cryptic by conventional methods were uncovered in approximately 34% of patients. This led to changes in the R-IPSS score for 17% of patients, improving prognostic prediction.26 Similarly, in another real-world, multicenter AML study, OGM uncovered cryptic translocations in 6.3% of AML cases with normal CG and 15.4% with abnormal CG. OGM results also altered the ELN classification in approximately 5% of patients with AML and identified opportunities for clinical trial enrollment in approximately 8% of patients.45 Notably, that study described another case of AML with inv(16) that went undetected by conventional methods but was clearly identified by OGM, further reinforcing its clinical value.45
OGM has limitations, particularly in resolving and interpreting ploidy and clonal architecture at the single-cell level. These challenges are common to all bulk DNA techniques, such as whole-genome sequencing. However, the superior ability of OGM to detect chromosomal structural abnormalities at the gene level across the genome eliminates the need for a reflex cascade of targeted FISH studies, dramatically reducing both cost and turnaround time.40,41 Although OGM is not yet widely available, it is rapidly being adopted in genetic laboratories due to its ease of implementation, short turnaround time, and relatively simple in-built bioinformatics pipeline for analysis.40
Beyond this, clinical questions remain regarding whether a “late diagnosis” of inv(16) following hypomethylating agent therapy would preclude a patient’s eligibility for AML treatment protocols, and what the optimal strategies for monitoring these patients after treatment would be. Further studies on genome-wide, high-coverage MRD assays are needed to address these questions.
Conclusions
This case highlights the ability of OGM to uncover a previously undetected, clinically significant, and actionable inv(16)/CBFB::MYH11 genomic aberration, consistent with a diagnosis of CBFB::MYH11-rearranged AML, in a patient initially misdiagnosed with t-MDS and treated with suboptimal therapy. The discovery of a novel CBFB::MYH11 transcript with noncanonical breakpoints, identified through OGM, exposes a critical diagnostic blind spot even when using a combination of current standard-of-care methods. This finding underscores the importance of adopting OGM as a first-tier diagnostic tool for comprehensive assessment of cytogenetic aberrations to identify actionable alterations that can guide personalized therapies. Prospective studies are needed to evaluate the clinical outcomes of patients with AML assessed with OGM.
References
- 1.↑
Liu P, Tarlé SA, Hajra A, et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 1993;261:1041–1044.
- 2.↑
Faber ZJ, Chen X, Gedman AL, et al. The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 2016;48:1551–1556.
- 3.↑
Duployez N, Marceau-Renaut A, Boissel N, et al. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood 2016;127:2451–2459.
- 4.↑
Gandhi V, Estey E, Keating MJ, et al. Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 1993;11:116–124.
- 5.↑
Boddu P, Gurguis C, Sanford D, et al. Response kinetics and factors predicting survival in core-binding factor leukemia. Leukemia 2018;32:2698–2701.
- 6.↑
Borthakur G, Kantarjian H. Core binding factor acute myelogenous leukemia-2021 treatment algorithm. Blood Cancer J 2021;11:114.
- 7.↑
Arthur D, Bloomfield C. Partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute nonlymphocytic leukemia: a new association. Blood 1983;61:994–998.
- 8.↑
Quesada AE, Luthra R, Jabbour E, et al. Incidental identification of inv(16)(p13.1q22)/CBFB-MYH11 variant transcript in a patient with therapy-related acute myeloid leukemia by routine leukemia translocation panel screen: implications for diagnosis and therapy. Cold Spring Harb Mol Case Stud 2021;7:a006084.
- 9.↑
Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood 2022;140:1200–1228.
- 10.↑
Khoury JD, 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;36:1703–1719.
- 11.↑
Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140:1345–1377.
- 12.↑
Borthakur G, Kantarjian H, Wang X, et al. Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer 2008;113:3181–3185.
- 13.↑
Borthakur G, Cortes JE, Estey EE, et al. Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol 2014;89:964–968.
- 14.↑
Bloomfield CD, Lawrene D, Byrd JD, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 1998;58:4173–4179.
- 15.↑
Loke J, Buka R, Craddock C. Allogeneic stem cell transplantation for acute myeloid leukemia: who, when, and how? Front Immunol 2021;12:659595.
- 16.↑
Pollyea DA, Bixby D, Perl A, et al. NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021. J Natl Compr Canc Netw 2021;19:16–27.
- 17.↑
Langabeer SE, Walker H, Gale RE, et al. Frequency of CBFβ/MYH11 fusion transcripts in patients entered into the U.K. MRC AML trials. Br J Haematol 1997;96:736–739.
- 18.↑
Moorman AV, Harrison CJ, Buck GAN, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 2007;109:3189–3197.
- 19.↑
Hernández JM, González MB, Granada I, et al. Detection of inv(16) and t(16;16) by fluorescence in situ hybridization in acute myeloid leukemia M4Eo. Haematologica 2000;85:481–485.
- 20.↑
Akkari YMN, Baughn LB, Dubuc AM, et al. Guiding the global evolution of cytogenetic testing for hematologic malignancies. Blood 2022;139:2273–2284.
- 21.↑
Wheeler FC, Kim AS, Mosse CA, et al. Limited utility of fluorescence in situ hybridization for recurrent abnormalities in acute myeloid leukemia at diagnosis and follow-up. Am J Clin Pathol 2018;149:418–424.
- 22.↑
Rack KA, van den Berg E, Haferlach C, et al. European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia 2019;33:1851–1867.
- 23.↑
van der Reijden BA, Lombardo M, Dauwerse HG, et al. RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts. Blood 1995;86:277–282.
- 24.↑
Barseghyan H, Tang W, Wang RT, et al. Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis. Genome Med 2017;9:90.
- 25.↑
Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454–2465.
- 26.↑
Yang H, Garcia-Manero G, Sasaki K, et al. High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance. Leukemia 2022;36:2306–2316.
- 27.↑
Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002;100:4325–4336.
- 28.↑
Metzeler KH, Herold T, Rothenberg-Thurley M, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128:686–698.
- 29.↑
Takahashi K, Wang F, Kantarjian H, et al. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. Lancet Oncol 2017;18:100–111.
- 30.↑
Liu PP, Wijmenga C, Hajra A, et al. Identification of the chimeric protein product of the CBFB-MYH11 fusion gene in inv(16) leukemia cells. Genes Chromosomes Cancer 1996;16:77–87.
- 31.↑
Bueso-Ramos CE, Kanagal-Shamanna R, Routbort MJ, et al. Therapy-related myeloid neoplasms. Am J Clin Pathol 2015;144:207–218.
- 32.↑
Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov 2006;5:147–159.
- 33.↑
Appelbaum FR, Bernstein ID. Gemtuzumab ozogamicin for acute myeloid leukemia. Blood 2017;130:2373–2376.
- 34.↑
Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol 2014;15:986–996.
- 35.↑
Williams KM. Noninfectious lung complications of hematopoietic cell transplantation. Hematology Am Soc Hematol Educ Program 2021;2021:578–586.
- 36.↑
Bhatia S. Caring for the long-term survivor after allogeneic stem cell transplantation. Hematology Am Soc Hematol Educ Program 2014;2014:495–503.
- 37.↑
Buchbinder D, Khera N. Psychosocial and financial issues after hematopoietic cell transplantation. Hematology Am Soc Hematol Educ Program 2021;2021:570–577.
- 38.↑
Duncavage EJ, Schroeder MC, O’Laughlin M, et al. Genome sequencing as an alternative to cytogenetic analysis in myeloid cancers. N Engl J Med 2021;384:924–935.
- 39.↑
Au CH, Ho DN, Ip BBK, et al. Rapid detection of chromosomal translocation and precise breakpoint characterization in acute myeloid leukemia by nanopore long-read sequencing. Cancer Genet 2019;239:22–25.
- 40.↑
Smith AC, Neveling K, Kanagal-Shamanna R. Optical genome mapping for structural variation analysis in hematologic malignancies. Am J Hematol 2022;97:975–982.
- 41.↑
Levy B, Kanagal-Shamanna R, Sahajpal NS, et al. A framework for the clinical implementation of optical genome mapping in hematologic malignancies. Am J Hematol 2024;99:642–661.
- 42.↑
Gerding WM, Tembrink M, Nilius-Eliliwi V, et al. Optical genome mapping reveals additional prognostic information compared to conventional cytogenetics in AML/MDS patients. Int J Cancer 2022;150:1998–2011.
- 43.↑
Stinnett V, Jiang L, Haley L, et al. Adoption of optical genome mapping in clinical cancer cytogenetic laboratory: a stepwise approach. J Clin Anat Pathol 2021;6:117.
- 44.↑
Neveling K, Mantere T, Vermeulen S, et al. Next-generation cytogenetics: comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping. Am J Hum Genet 2021;108:1423–1435.
- 45.↑
Levy B, Baughn LB, Akkari Y, et al. Optical genome mapping in acute myeloid leukemia: a multicenter evaluation. Blood Adv 2023;7:1297–1307.
