RESUMO
We described four patients with diffuse large B-cell lymphoma (DLBCL) carrying t(9;14)(p13;q32) that places the PAX5 adjacent to the immunoglobulin heavy chain (IGH) gene. Ages ranged between 63 and 80, and three were female. One developed a nodal disease, and the other three involved extranodal organs. The lymphoma cells were CD10- /BCL6- /MUM1+ in three and CD10+ /BCL6+ /MUM1+ in one. BCL2 was weak or negative. All had t(9;14)(p13;q32), and three had additional 14q32/IGH translocations or +der(14)t(9;14)(p13;q32). Fluorescence in situ hybridization using the PAX5 break-apart probe showed that the locus was disrupted between the 5' and 3' probes or within the 5' probe. Immunohistochemistry (IHC) using a monoclonal antibody against PAX5 showed strong nuclear positivity in all four patients. Cell block IHC of a CD30+ DLBCL cell line, KIS-1, which carried the t(9;14)(p13;q32) and PAX5-IGH fusion gene, reproduced the CD10- /BCL6- /MUM1+ immunophenotype, low-level BCL2, and strong nuclear PAX5. Uniform nuclear positivity of MUM1 in all four cases and KIS-1 cells suggest that these lymphomas arose at a late stage of B-cell differentiation, where expression of PAX5 physiologically becomes downregulated. It is therefore possible that high-level PAX5 resulting from t(9;14)(p13;q32) at this stage of differentiation perturbs the plasma cell differentiation program initiated by PAX5 repression, thereby contributing to the development of a fraction of DLBCL.
Assuntos
Núcleo Celular/metabolismo , Cadeias Pesadas de Imunoglobulinas/genética , Imuno-Histoquímica/métodos , Fatores Reguladores de Interferon/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Fator de Transcrição PAX5/metabolismo , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 9/genética , Feminino , Humanos , Fatores Reguladores de Interferon/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Transcrição PAX5/genética , PrognósticoRESUMO
We describe the establishment and characterization of a cell line, AM-HLH, obtained from a patient with Epstein-Barr virus-positive (EBV+ ) nodular sclerosis-type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy- and κ light-chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV-encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2). Fluorescence in situ hybridization (FISH) with the cosmid pJB8 clone containing a fragment of EBV DNA as a probe revealed multiple hybridization signals at a marker chromosome. Additional FISH using whole chromosome painting and centromere probes in combination with multicolor FISH determined that multiple EBV copies were clustered within the chromosome 20 materials of the marker chromosome. Culture supernatants of AM-HLH contained IL-10 as measured by the bead-based immunoassay. It is possible that an integrated EBV genome and cellular genes on chromosome 20 were coamplified, leading to the enhanced expression of genes involved in cell growth control. The AM-HLH cell line will be useful to clarify the role of cytokines in the development of EBV+ HL.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Genoma Viral , Herpesvirus Humano 4/genética , Doença de Hodgkin/etiologia , Doença de Hodgkin/patologia , Integração Viral , Idoso , Biomarcadores , Linhagem Celular Tumoral , Bandeamento Cromossômico , Interações Hospedeiro-Patógeno , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , FenótipoRESUMO
We describe two types of IGH::BCL2 breakpoints involving the 5' region of BCL2 (5' BCL2). One was ins(14;18)(q32;q21q21) observed in 2 follicular lymphoma (FL) cases, in which IGH was cleaved at 3' of IGHD and 5' of IGHJ and BCL2 was cleaved at 5' BCL2 and downstream regions, and a 281- or 201-kilobase pair fragment containing the BCL2 protein-coding sequences was invertedly inserted into IGH. In another type observed in 2 FL and 2 chronic lymphocytic leukemia (CLL) cases, breakage and reunion occurred within the switch region associated with IGHM (Sµ) and 5' BCL2, creating IGH Sµ::5' BCL2 fusion sequences on der(18)t(14;18)(q32;q21). The former is considered to be mediated by VDJ-recombination, while the latter by the class switch recombination process. There were no particular features in FL or CLL cases with IGH::5' BCL2 breakpoints compared with those with t(14;18)(q32;q21)/IGH::BCL2 involving the 3' breakpoint cluster regions.
Assuntos
Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Cadeias Pesadas de Imunoglobulinas , Proteínas Proto-Oncogênicas c-bcl-2 , Translocação Genética , Humanos , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Cadeias Pesadas de Imunoglobulinas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Switching de Imunoglobulina/genética , Recombinação V(D)J/genética , Linfoma Folicular/genética , Linfoma Folicular/patologia , Pessoa de Meia-Idade , Masculino , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Feminino , Hibridização in Situ Fluorescente , IdosoRESUMO
We characterized 5 B-cell tumors carrying t(14;19)(q32;q13) that creates the IGH::BCL3 fusion gene. The patients' ages ranged between 55 and 88 years. Two patients presented with progression or recurrence of B-cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL), two with diffuse large B-cell lymphoma (DLBCL) of non-germinal center B-like phenotype, and the remaining one with composite angioimmunoblastic T-cell lymphoma and Epstein-Barr virus-positive DLBCL. The presence of t(14;19)(q32;q13) was confirmed by fluorescence in situ hybridization (FISH), showing colocalization of 3' IGH and 3' BCL3 probes on der(14)t(14;19) and 5' BCL3 and 5' IGH probes on der(19)t(14;19). One B-CLL case had t(2;14)(p13;q32)/IGH::BCL11A, and 2 DLBCL cases had t(8;14)(q24;q32) or t(8;11;14)(q24;q11;q32), both of which generated IGH::MYC by FISH, and showed nuclear expression of MYC and BCL3 by immunohistochemistry. The IGH::BCL3 fusion gene was amplified by long-distance polymerase chain reaction in 2 B-CLL/SLL cases and the breakpoints occurred immediately 5' of BCL3 exon 1 and within the switch region associated with IGHA1. The 5 cases shared IGHV preferentially used in B-CLL cells, but the genes were unmutated in 2 B-CLL/SLL cases and significantly mutated in the remaining 3. B-cell tumors with t(14;19)(q32;q13) can be divided into B-CLL/SLL and DLBCL groups, and the anatomy of IGH::BCL3 in the latter may be different from that of the former.
Assuntos
Infecções por Vírus Epstein-Barr , Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Hibridização in Situ Fluorescente , Translocação Genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/genética , Cromossomos Humanos Par 14/genéticaRESUMO
We describe two follicular lymphoma (FL) patients with MYC/BCL2 double- and MYC/BCL2/BCL6 triple-hit translocations. The first patient (case 1) was a man in his 30s who presented with stage IV disease with leukemic manifestation. The second patient (case 2) was a man in his 60s who presented with relapsed FL, but his disease was in a limited stage. Histopathology of the lymph node biopsies revealed grade 3A FL in both cases. MYC positivity and the Ki-67-labeling index were 60-70 and 20% in case 1 and 30 and 50% in case 2, respectively. G-banding revealed t(8;14;18)(q24;q32;q21) in both cases and fluorescence in situ hybridization using MYC, IGH, and BCL2 break-apart probes confirmed t(8;14;18)(+5'BCL2,-3'MYC;+3'MYC,-5'IGH;+5'IGH,-5'BCL2). In case 2, additional materials of der(8)t(8;14;18) were duplicated and translocated to chromosome Y, and t(3;16)(q27;p13)/BCL6::CIITA was identified. We obtained BCL2-major breakpoint region::IGHJ5::IGHG1 and MYC exon 2::IGHA2 fusion sequences by long-distance polymerase chain reaction in case 1, and proposed that t(8;14;18) was generated by two-step translocations and that BCL2::IGH and MYC::IGH involved the same IGH allele. Both patients responded to the standard chemotherapy for FL. We suggest that the presence of t(8;14;18) in FL does not immediately indicate high-grade transformation and aggressive clinical behavior requiring intensive chemotherapy.
Assuntos
Linfoma de Células B , Linfoma Folicular , Humanos , Masculino , Hibridização in Situ Fluorescente , Linfoma de Células B/patologia , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Adulto , Pessoa de Meia-IdadeRESUMO
We describe two patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL). The first patient (case 1) was a woman in her late 70s who presented with a tumor in the left frontal lobe, whereas the second patient (case 2) was a man in his early 70s who presented with a left frontal lobe tumor associated with intratumoral hemorrhage. The histopathology of the tumor specimen disclosed the proliferation of large cells with centroblastic (case 1) or immunoblastic/plasmablastic (case 2) cytomorphology and an accumulation of the tumor cells within the perivascular space. The cells in both cases were positive for CD20, CD79a, BCL6, IRF4/MUM1, MYC, and BCL2 and negative for CD5 and CD10. G-banding revealed t(8;14)(q24;q32) in case 1, and the tetraploid-range karyotype including two or three copies of der(3)t(3;14)(q27;q32) and der(14)t(3;14)(q27;q32) in case 2. Fluorescence in situ hybridization applied to metaphase spreads confirmed colocalization of MYC and IGH (case 1) and BCL6 and IGH (case 2) hybridization signals on the relevant derivative chromosomes. Case 1 carried the MYD88L265P mutation. This case report provides clear evidence for the occurrence of t(8;14)(q24;q32) and t(3;14)(q27;q32) in PCNS-DLBCL using metaphase-based cytogenetic analysis.
Assuntos
Linfoma Difuso de Grandes Células B , Translocação Genética , Masculino , Feminino , Humanos , Hibridização in Situ Fluorescente , Metáfase , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Mutação , Cromossomos Humanos Par 14/genéticaRESUMO
A 75-year-old man presented with an ileocecal tumor composed of diffuse proliferation of large cells with immunoblastic morphology. Lymphoma cells were positive for CD20, CD79a, IRF4/MUM1, and BCL2, negative for CD5, CD10, and MYC, and partially positive for BCL6. PAX5 was positive with variable staining intensity among the cell nuclei. The V-D-J sequence of IGH showed the mutated configuration. The G-banding karyotype demonstrated two cytogenetic clones with or without t(9;14)(p13;q32), but the two shared other structural and numerical abnormalities. Fluorescence in situ hybridization using PAX5 and IGH probes confirmed the presence or absence of t(9;14)(p13;q32)/PAX5-IGH in each clone. The breakpoints of t(9;14)(p13;q32) were mapped 2,170 bp upstream of the coding region of PAX5 alternative exon 1B and within the IGHJ6-Eµ enhancer intron of IGH. It is suggested that t(9;14)(p13;q32) in this case was a secondary cytogenetic abnormality and the translocation is not necessarily involved in initial malignant transformation of B-cells but can occur later during the course of diffuse large B-cell lymphoma.
Assuntos
Proteínas de Ligação a DNA , Linfoma Difuso de Grandes Células B , Idoso , Transformação Celular Neoplásica , Cromossomos Humanos Par 14/genética , Proteínas de Ligação a DNA/genética , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Masculino , Fator de Transcrição PAX5/genética , Translocação GenéticaRESUMO
An 80-year-old man presented with the accumulation of pleural fluid in the right thoracic cavity. Serum electrophoresis revealed an M-component and immunofixation confirmed IgM/λ. The level of IgM was 1,526 mg/dL. Imaging studies showed an infiltrative condition of the ipsilateral lung parenchyma. The fluid contained abundant neoplastic cells with the morphological and immunophenotypic features of plasma cells, which expressed IgM/λ monoclonal immunoglobulins on the cell surface and in the cytoplasm. The karyotype was 48,XY,+3,add(9)(p13),+12,add(14)(q32),del(16)(q22),-18,+mar, and a series of fluorescence in situ hybridization studies demonstrated that the add(14) chromosome represented der(14)t(14;18)(q32;q21), at which the MALT1-immunoglobulin heavy-chain (IGH) fusion gene was localized. A long-distance polymerase chain reaction amplified the fragment encompassing the two genes, showing that the junction occurred at the J6 segment of IGH and 3.7-kb upstream of the MALT1 breakpoint cluster. We propose that this case represents an extreme form of the plasmacytic differentiation of extranodal marginal zone lymphoma that developed in the lung.
Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Cadeias Pesadas de Imunoglobulinas , Neoplasias Pulmonares , Linfoma de Zona Marginal Tipo Células B , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , Proteínas de Fusão Oncogênica , Plasmócitos , Cavidade Pleural , Translocação Genética , Macroglobulinemia de Waldenstrom , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/metabolismo , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Plasmócitos/metabolismo , Plasmócitos/patologia , Cavidade Pleural/metabolismo , Cavidade Pleural/patologia , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/metabolismo , Macroglobulinemia de Waldenstrom/patologiaRESUMO
CD4+CD56+ lineage negative malignancy has recently been considered as plasmacytoid dendritic cell (PDC) leukemia/lymphoma. We investigated immunophenotypic and functional characterizations of PDC leukemic cells in one case. Lineage markers were all negative except partially positive CD11c and positive CD117, indicating malignant cells were leukemic PDCs coexpressing myeloid and progenitor cell surface antigens. Leukemic PDCs cultured with IL-3 increased in size and expression of CD11c, CD40 and HLA-DR, although the cells cultured with IL-2 or GM-CSF showed little proliferation. Furthermore, CD40 ligation after IL-3 stimulation yielded morphological changes such as expression of dendritic process. These findings showed that malignant cells were consistent with leukemic PDCs. However, secretion of interferon-alpha was not detected in leukemic PDCs with the stimulation of CpG ODN or inactivated herpes simplex virus-1.
Assuntos
Antígenos CD/análise , Células Dendríticas/imunologia , Leucemia/imunologia , Idoso , Linhagem da Célula , Feminino , Humanos , Imunofenotipagem , Interferon-alfa/metabolismo , Leucemia/patologia , Linfocinas/imunologia , Linfocinas/metabolismoRESUMO
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region. As a result of t(14;15)(q32;q24), BCL2A1 and IGH Sγ4-Cγ4 were aligned in the same transcriptional orientation at a distance of 64 kb. Reverse transcriptase-mediated PCR showed high BCL2A1 mRNA levels in a lymphoma specimen. Since BCL2A1, mapped at 15q24.3 or 15q25.1, encodes a protein that is an anti-apoptotic member of the BCL2 protein family, we herein described the novel double-hit, t(8;22)(q24;q11)/MYC-IGL and t(14;15)(q32;q24)/IGH-BCL2A1, in which BCL2A1 is considered to play a role equivalent to that of BCL2 in the most frequent double-hit, MYC/BCL2.
Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Cadeias lambda de Imunoglobulina/genética , Linfoma Difuso de Grandes Células B/genética , Antígenos de Histocompatibilidade Menor/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 8 , Feminino , Humanos , Hibridização in Situ Fluorescente , CariótipoRESUMO
A 53-year-old woman was admitted to the department of neurology in Tenri Hospital because of progressive thoracic myelitis a month after she had eaten uncooked bovine liver. A previous episode of right optic neuritis and a positive test for serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica spectrum disorders. Although the patient initially recovered with the reduction of anti-aquaporin-4 antibodies during treatment with intravenous methylprednisolone infusion and plasma exchange, her neurological symptoms deteriorated soon after the completion of plasma exchange. Western blotting analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient underwent oral albendazole treatment. This resulted in the alleviation of her symptoms. We therefore consider that rigorous investigation should be encouraged to detect rare pathogens including parasites in cases of treatment-resistant neuromyelitis optica spectrum disorders.
Assuntos
Neuromielite Óptica/complicações , Toxocaríase/complicações , Albendazol/uso terapêutico , Anticorpos/sangue , Antiprotozoários/uso terapêutico , Aquaporina 4/imunologia , Resistência a Medicamentos , Feminino , Humanos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Toxocaríase/imunologiaRESUMO
This is the first report on the development of a p.G1269A mutation within the kinase domain (KD) of ALK after crizotinib treatment in RANBP2-ALK acute myeloid leukemia (AML). An elderly woman with AML with an inv(2)(p23q13)/RANBP2-ALK and monosomy 7 was treated with crizotinib. After a short-term hematological response and the restoration of normal hematopoiesis, she experienced a relapse of AML. Fluorescence in situ hybridization using the ALK break-apart probe confirmed the inv(2)(p23q13), while G-banded karyotyping revealed the deletion of a segment of the short arm of chromosome 1 [del(1)(p13p22)] after crizotinib therapy. The ALK gene carried a heterozygous mutation at the nucleotide position g.716751G>C within exon 25, causing the p.G1269A amino acid substitution within the ALK-KD. Reverse transcriptase PCR revealed that the mutated ALK allele was selectively transcribed and the mutation occurred in the ALK allele rearranged with RANBP2. As both the del(1)(p13p22) at the cytogenetic level and p.G1269A at the nucleotide level newly appeared after crizotinib treatment, it is likely that they were secondarily acquired alterations involved in crizotinib resistance. Although secondary genetic abnormalities in ALK are most frequently described in non-small cell lung cancers harboring an ALK alteration, this report suggests that an ALK-KD mutation can occur independently of the tumor cell type or fusion partner after crizotinib treatment.
Assuntos
Deleção Cromossômica , Inversão Cromossômica , Cromossomos Humanos Par 2 , Leucemia Mieloide Aguda/genética , Chaperonas Moleculares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Idoso , Quinase do Linfoma Anaplásico , Cromossomos Humanos Par 7 , Crizotinibe , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas Recombinantes de Fusão/genéticaRESUMO
In anaplastic large cell lymphoma (ALCL), the anaplastic lymphoma kinase (ALK) gene is rearranged with diverse partners due to variant translocations/inversions. Case 1 was a 39-year-old man who developed multiple tumors in the mediastinum, psoas muscle, lung, and lymph nodes. A biopsy specimen of the inguinal node was effaced by large tumor cells expressing CD30, epithelial membrane antigen, and cytoplasmic ALK, which led to a diagnosis of ALK(+) ALCL. Case 2 was a 51-year-old man who was initially diagnosed with undifferentiated carcinoma. He developed multiple skin tumors eight years after his initial presentation, and was finally diagnosed with ALK(+) ALCL. He died of therapy-related acute myeloid leukemia. G-banding and fluorescence in situ hybridization using an ALK break-apart probe revealed the rearrangement of ALK and suggested variant translocation in both cases. We applied an inverse cDNA polymerase chain reaction (PCR) strategy to identify the partner of ALK. Nucleotide sequencing of the PCR products and a database search revealed that the sequences of ATIC in case 1 and TRAF1 in case 2 appeared to follow those of ALK. We subsequently confirmed ATIC-ALK and TRAF1-ALK fusions by reverse transcriptase PCR and nucleotide sequencing. We successfully determined the partner gene of ALK in two cases of ALK(+) ALCL. ATIC is the second most common partner of variant ALK rearrangements, while the TRAF1-ALK fusion gene was first reported in 2013, and this is the second reported case of ALK(+) ALCL carrying TRAF1-ALK.
Assuntos
Linfoma Anaplásico de Células Grandes/genética , Receptores Proteína Tirosina Quinases/genética , Translocação Genética , Adulto , Quinase do Linfoma Anaplásico , DNA Complementar/análise , DNA Complementar/genética , Humanos , Hibridização in Situ Fluorescente , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
A 75-year-old woman presented with marked leukocytosis; the white cell count was 143.6 × 10³/µL with 38.6 % monocytes and 13.6 % immature granulocytes, including blasts. Bone marrow (BM) aspirate smears showed >90 % cellularity with hyperplasia of myeloid-lineage cells, 14.6 % monocytes, and 32.1 % blasts. The granulocyte series showed a range of dysplastic morphologies. The rate of peroxidase positivity was 51.5 %. CD36+ cells with monocytic differentiation comprised 64.6 % mononuclear cells. Metaphase spreads obtained from the BM revealed an aneuploid karyotype with -7 and a submetacentric marker chromosome derived from chromosome 2, which was determined to be inv(2)(p23q13) by fluorescence in situ hybridization using the Vysis ALK probe. RAN-binding protein 2 (RANBP2)-ALK fusion mRNA was confirmed by reverse transcriptase-mediated polymerase chain reaction and nucleotide sequencing. High-sensitivity anti-ALK immunohistochemistry of a BM biopsy specimen demonstrated nuclear membrane staining of leukemia cells. As the leukemia showed features of chronic myelomonocytic leukemia, the patient was treated with standard daunorubicin-cytarabine followed by azacitidine, leading to the durable suppression of leukemia progression. These findings suggest that inv(2)(p23q13)/RABBP2-ALK defines a small subset of myeloid leukemia characterized by differentiation to monocytes and sharing features of myelodysplastic syndrome/myeloproliferative neoplasm.