ABSTRACT
BACKGROUND: Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM). METHODS: The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified. RESULTS: Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route. CONCLUSION: The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
Subject(s)
Immune Checkpoint Inhibitors , Liver Neoplasms , Myeloid-Derived Suppressor Cells , Animals , Mice , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Humans , Drug Delivery Systems , Mice, Inbred C57BL , Cell Line, TumorABSTRACT
Among diffuse large b-cell lymphoma (DLBCL) subtypes, primary testicular lymphoma (PTL) has one of the highest risks of central nervous system (CNS) relapse. The converse, primary CNS lymphoma (PCNSL) relapse outside the CNS is rare. Molecular analysis has illustrated a genetic similarity between PTL and PCNSL. Here we present a case of a 64-year-old man with testicular relapse of PCNSL 20 months after a complete response to high dose methotrexate-based chemotherapy. His tumor demonstrated a molecular profile similar to both PCNSL and PTL on next generation sequencing, and molecular analysis confirmed common clonal origin of his CNS and testicular lesions. We review prior cases of testicular relapse of PCNSL, which lacked molecular investigations, and discuss the implications of the genomic findings in our patient, including future treatment options.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Male , Humans , Middle Aged , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Central Nervous System , Chronic Disease , GenomicsABSTRACT
While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2 (SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM stroma. Enrichment of osteoblast maturation-related transcripts of biglycan (BGN), osteopontin (SPP1) and osteonectin (SPARC) was observed in non-responders. To the best of our knowledge, this is the first report demonstrating distinct osteogenic and mesenchymal transcriptome profiles specific to AML response to induction chemotherapy assessed directly in core BM biopsies. Detailing treatment response-specific alterations in the BM stroma may inform optimised therapeutic strategies for AML.
Subject(s)
Bone Marrow , Leukemia, Myeloid, Acute , Humans , Bone Marrow/pathology , Transcriptome , Leukemia, Myeloid, Acute/drug therapy , Cytarabine/therapeutic use , Bone Marrow Cells/pathology , Anthracyclines/therapeutic use , Biopsy , Tumor MicroenvironmentABSTRACT
GSK-3ß is a serine/threonine kinase implicated in tumorigenesis and chemotherapy resistance. GSK-3ß blockade downregulates the NF-κB pathway, modulates immune cell PD-1 and tumor cell PD-L1 expression, and increases CD8 + T cell and NK cell function. We report a case of adult T-cell leukemia/lymphoma (ATLL) treated with 9-ING-41, a selective GSK-3ß inhibitor in clinical development, who achieved a durable response. A 43-year-old male developed diffuse lymphadenopathy, and biopsy of axillary lymph node showed acute-type ATLL. Peripheral blood flow cytometry revealed a circulating clonal T cell population, and CSF was positive for ATLL involvement. After disease progression on the 3rd line of treatment, he started treatment with 9-ING-41 monotherapy in a clinical trial (NCT03678883). CT imaging after seven months showed a partial response. Sustained reduction of peripheral blood ATLL cells lasted 15 months. Treatment of patient-derived CD8 + T cells with 9-ING-41 increased the secretion of IFN-γ, granzyme B, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In conclusion, treatment of a patient with refractory ATLL with the GSK-3ß inhibitor 9-ING-41 resulted in a prolonged response. Ongoing experiments are investigating the hypothesis that 9-ING-41-induced T cell activation and immunomodulation contributes to its clinical activity. Further clinical investigation of 9-ING-41 for treatment of ATLL is warranted.
Subject(s)
Leukemia-Lymphoma, Adult T-Cell , Lymphoma , Adult , Apoptosis , Glycogen Synthase Kinase 3 beta , Humans , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Male , NF-kappa B/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)-based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis.
Subject(s)
Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Biomarkers , Central Nervous System , DNA , HumansSubject(s)
Central Nervous System Neoplasms/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Neoplasm Recurrence, Local/genetics , Aged , Aged, 80 and over , Central Nervous System Neoplasms/pathology , Female , Gene Rearrangement , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local/pathology , Risk FactorsABSTRACT
ABSTRACT: Mycosis fungoides (MF) is primarily characterized by epidermotropic CD3+/CD4+/CD45RO+ memory T cells. CD4/CD8 double-negative MF is an uncommon variant with no presumed prognostic significance. Despite the variability in the clinical course and presentation of MF, most cases behave indolently. About 5% of patients, however, advance to stage IV with visceral organ involvement. Central nervous system metastasis in MF is rare with no known cases of direct central nervous system invasion by MF to date. We report an exceedingly rare locally aggressive case of CD4/CD8 double-negative MF with direct dural invasion and underline pertinent diagnostic challenges encountered in our case.
Subject(s)
Dura Mater/pathology , Head and Neck Neoplasms/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/pathology , Scalp/pathology , Skin Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Dura Mater/immunology , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/therapy , Humans , Lymphoma, T-Cell, Cutaneous/genetics , Lymphoma, T-Cell, Cutaneous/immunology , Lymphoma, T-Cell, Cutaneous/therapy , Mycosis Fungoides/genetics , Mycosis Fungoides/immunology , Mycosis Fungoides/therapy , Neoplasm Invasiveness , Scalp/immunology , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Skin Neoplasms/therapy , Treatment OutcomeABSTRACT
Although the pathogenesis of primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell-eradicating potential, indicating that other targetable mechanisms are contributing to the pathophysiology of MPNs. We previously demonstrated that Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions as a tumor suppressor. Here we present data showing that bone marrow-specific deletion of Abi1 in a novel mouse model leads to development of an MPN-like phenotype resembling human PMF. Abi1 loss resulted in a significant increase in the activity of the Src family kinases (SFKs), STAT3, and NF-κB signaling. We also observed impairment of hematopoietic stem cell self-renewal and fitness, as evidenced in noncompetitive and competitive bone marrow transplant experiments. CD34+ hematopoietic progenitors and granulocytes from patients with PMF showed decreased levels of ABI1 transcript as well as increased activity of SFKs, STAT3, and NF-κB. In aggregate, our data link the loss of Abi-1 function to hyperactive SFKs/STAT3/NF-κB signaling and suggest that this signaling axis may represent a regulatory module involved in the molecular pathophysiology of PMF.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Bone Marrow/pathology , Cytoskeletal Proteins/genetics , Gene Deletion , Primary Myelofibrosis/genetics , Primary Myelofibrosis/pathology , Animals , Bone Marrow/metabolism , Cell Self Renewal , Cells, Cultured , Down-Regulation , Female , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , NF-kappa B/metabolism , Primary Myelofibrosis/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , src-Family Kinases/metabolismABSTRACT
The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential. Using quantitative phosphoproteomic analysis of these IM-resistant cells, we have now identified significant upregulation of tumor progression locus (Tpl2), also known as cancer Osaka thyroid (COT1) kinase or Map3k8. Overexpression of Tpl2 in IM-resistant cells was accompanied by elevated activities of Src family kinases (SFKs) and NF-κB, MEK-ERK signaling. CD34+ cells isolated from the bone marrow of patients with CML and exposed to IMin vitro showed increased MAP3K8 transcript levels. Dasatinib (SFK inhibitor), U0126 (MEK inhibitor), and PS-1145 (IκB kinase (IKK) inhibitor) used in combination resulted in elimination of 65% of IM-resistant cells and reduction in the colony-forming capacity of CML CD34+ cells in methylcellulose assays by 80%. In addition, CML CD34+ cells cultured with the combination of inhibitors showed reduced MAP3K8 transcript levels. Overall, our data indicate that elevated Tpl2 protein and transcript levels are associated with resistance to IM and that combined inhibition of SFK, MEK, and NF-κB signaling attenuates the survival of IM-resistant CML cells and CML CD34+ cells. Therefore, combination of SFK, MEK, and NF-κB inhibitors may offer a new therapeutic approach to overcome TKI resistance in CML patients.
Subject(s)
Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , Proto-Oncogene Proteins/metabolism , Animals , Cell Line, Tumor , Disease Models, Animal , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl/metabolism , Humans , Imatinib Mesylate/pharmacology , Models, Biological , Phosphopeptides/metabolism , Proteomics , Signal Transduction , src-Family Kinases/metabolismABSTRACT
Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas. These tumors primarily occur in peripheral soft tissues, but examples have been described within viscera and the brain. As far as we are aware, CIC-DUX4 positive primary epidural spinal sarcoma has not been reported. Herein, we describe a T5-T6 epidural tumor in a 15-year-old girl in which many neoplastic cells had moderate and focally abundant cytoplasm, including plasmacytoid or rhabdoid cells, rather than the more common Ewing-like morphology described in the majority of such tumors. The diagnosis was confirmed by fluorescent in situ hybridization after the tumor was found to be WT-1 positive, and comprehensive genomic profiling demonstrated breakpoints in exon 20 and exon 1 of the CIC and DUX4 genes, respectively. After treatment with local radiation and systemic chemotherapy, resected recurrent tumor demonstrated more pleomorphic neoplastic cells as well as intracytoplasmic eosinophilic globules and nuclear pseudoinclusions which may reflect therapy-related changes. Unfortunately, there was further progression of tumor including the development of intracranial lesions, and the patient succumbed to her tumor 22 months after the original resection.
Subject(s)
Biomarkers, Tumor/genetics , Epidural Neoplasms/diagnosis , Oncogene Proteins, Fusion/genetics , Sarcoma/diagnosis , Adolescent , Epidural Neoplasms/genetics , Epidural Neoplasms/pathology , Fatal Outcome , Female , Humans , Oncogene Fusion , Sarcoma/genetics , Sarcoma/pathology , Thoracic VertebraeABSTRACT
Hemoglobin (Hb) Sherwood Forest is a rare high-affinity hemoglobin first described in 1977, arising from an Arg to Thr substitution at codon 104 of the beta chain. This hemoglobin variant has been identified in few individuals and has been associated with a compensatory erythrocytosis in the homozygous state. Prior scarce case reports have noted that heterozygotes for this variant are phenotypically normal. Here we present a patient who was evaluated in our hematology clinic for chronic erythrocytosis and was found to be heterozygous for Hb Sherwood Forest. No other primary or secondary cause of his polycythemia was identified. This is the first described case of heterozygous Hemoglobin Sherwood Forest causing erythrocytosis.
ABSTRACT
An elderly woman with a complex medical history presented with a left forearm mass that slowly developed for several months. The excisional biopsy of this skin mass was remarkable for involvement by a follicle centre cell derived lymphoma with a nodular and diffuse pattern associated with a subset of scattered Hodgkin and Reed-Sternberg like cells. Fluorescence in situ hybridization studies did not detect the presence of IgH-bcl2 fusion transcript, and molecular studies were negative for immunoglobulin heavy chain gene rearrangements and EBV DNA sequences. Hodgkin and Reed-Sternberg like cells are rarely reported in FLs, and the association with primary cutaneous follicle centre lymphoma is extremely rarely seen. To our knowledge, our case is the second case of primary cutaneous follicle centre lymphoma with Hodgkin and Reed-Sternberg like cells.
ABSTRACT
Despite the success of tyrosine kinase inhibitor (TKI) therapy in chronic myelogenous leukemia (CML), leukemic stem/progenitor cells remain detectable even in the state of deep molecular remission. Mechanisms that allow them to persist despite continued kinase inhibition remain unclear. We have previously shown that prolonged exposure to imatinib mesylate (IM) results in dysregulation of Akt/Erk 1/2 signaling, upregulation of miR-181a, enhanced adhesiveness, and resistance to high IM. To characterize the molecular basis and reversibility of those effects, we applied gene and protein expression analysis, quantitative phosphoproteomics, and direct miR-181a inhibition to our cellular model of CML cells subjected to prolonged exposure to IM. Those cells demonstrated upregulation of pluripotency markers (SOX2, SALL4) and adhesion receptors (CD44, VLA-4, CXCR4), as well as downregulation of Hippo signaling and upregulation of transcription coactivator YAP. Furthermore, inhibition of miR-181a using a microRNA sponge inhibitor resulted in decreased transcription of SOX2 and SALL4, decreased activation of YAP, and increased sensitivity to IM. Our findings indicate that long-term exposure to IM results in dysregulation of stem cell renewal-regulatory Hippo/YAP signaling, acquisition of expression of stem cell markers and that experimental interference with YAP activity may help to restore chemosensitivity to TKI.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Down-Regulation/drug effects , Imatinib Mesylate/pharmacology , Phosphoproteins/genetics , Protein Serine-Threonine Kinases/genetics , Signal Transduction/drug effects , Adaptor Proteins, Signal Transducing/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Leukemic/drug effects , Hippo Signaling Pathway , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , MicroRNAs/genetics , Phosphoproteins/metabolism , Platelet Glycoprotein GPIb-IX Complex/genetics , Platelet Glycoprotein GPIb-IX Complex/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/metabolism , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Signal Transduction/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , YAP-Signaling ProteinsABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and highly aggressive subtype of non-Hodgkin's lymphoma. It commonly presents as rapidly-growing, painless lymphadenopathy (LAD). DLBCL presenting in leukemic-phase is rare, with fewer than 40 cases published. Chemotherapy remains the standard approach, although selecting the correct regimen has become more perplexing in patients with CDKN2A mutations. Patients with MLL- and CDKN2A-positive DLBCL may benefit from therapy with a dose-adjusted regimen of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) compared to traditional rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Herein, we report a case of leukemic-phase DLBCL presenting as a cutaneous eruption of the bilateral lower extremities, which has not been previously reported in the literature.
ABSTRACT
We present a 59-year-old male with poorly controlled celiac disease (CD) and fatal Streptococcus pneumoniae sepsis, describe the morphologic findings, and stress the need for monitoring splenic function and pneumococcal vaccination in these patients.
ABSTRACT
TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castleman's disease. Previous reports include various different treatment protocols with inconsistent survival outcomes. Here we report the first known American, EBV positive but HIV and HHV-8 negative, male with TAFRO syndrome. He was successfully treated with an unusual three-drug regimen including tocilizumab, etoposide, and rituximab. We review the literature of TAFRO syndrome, discuss its possible viral etiology, and propose an original treatment regimen.
ABSTRACT
BACKGROUND CONTEXT: Propionibacterium acnes is a gram-positive and facultative anaerobe bacillus that is found within sebaceous follicles of the human skin and recognized as a cause of infections after spinal surgery. To our knowledge, there has been no previously reported case of symptomatic compressive chronic inflammatory epidural mass caused by P. acnes in a patient with no prior spinal procedures. PURPOSE: This study aimed to describe a case of primary spinal infection by P. acnes. STUDY DESIGN: This study is a case report of a condition not previously described in the literature. METHODS: We present the history, physical examination, laboratory, radiographic, and histopathologic findings of a chronic inflammatory epidural mass caused by P. acnes in an immunocompetent adult male with no history of spinal surgery. RESULTS: A 51-year-old man presented to our clinic with sudden onset bilateral lower extremity weakness, inability to ambulate, and urinary retention. His past clinical history was remarkable only for hernia and left knee surgery but no spinal surgery. A year earlier, he had an infected draining abscess of the right axilla that was successfully managed medically. At presentation, his serum erythrocyte sedimentation rate and C-reactive protein were moderately elevated. Pan-spine magnetic resonance imaging was notable for a circumferential epidural mass from C5 to T6. He underwent emergent decompression; the mass was removed and sent for culture and pathologic evaluation. Cultures from all three specimens collected during surgery grew P. acnes, and the patient was successfully managed on intravenous ceftriaxone, while pathology revealed a chronic inflammatory reactive process. CONCLUSIONS: This is the first reported case of a primary spinal mass with chronic inflammatory features caused by P. acnes. In cases of epidural mass of unknown origin, both pathologic specimens and cultures should be obtained as slow-growing organisms may mimic oncologic processes.
Subject(s)
Bacterial Infections/pathology , Epidural Space/microbiology , Propionibacterium acnes/pathogenicity , Spinal Cord Compression/pathology , Bacterial Infections/diagnostic imaging , Bacterial Infections/microbiology , Epidural Space/pathology , Humans , Male , Middle Aged , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/microbiologyABSTRACT
Acute myeloid leukemia with inv3(q21q26.2)/t(3,3)(q21;q26.2) is a subtype of acute myeloid leukemia associated with significant dysmyelopoiesis and a poor prognosis. In more than a half of the cases, there is also monosomy 7. We present 2 young male patients with de novo acute myeloid leukemia with inversion 3 and monosomy 7 who had significant morphologic and immunophenotypical similarities. Both patients had circulating subsets of blasts with unusual intracytoplasmic basophilic granules and prominent bone marrow dysmegakaryopoiesis. The leukemic myeloid blasts were negative for myeloperoxidase and had aberrant coexpression of CD2 and CD31. Despite their morphologic and immunophenotypical similarities, only 1 of the patients achieved remission and remained free of disease 24 months after bone marrow transplant. The younger patient, who had also increased hemoglobin F and an associated FLT3 D835 variant, had an acute myeloid leukemia refractory to chemotherapy and died 4 months after his diagnosis.