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To the editor: Calreticulin ( CALR ) mutations have been reported primarily in the context of JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis.[1][1][⇓][2][⇓][3][⇓][4]-[5][5] CALR mutations are exceedingly rare in the setting of t(9;22)/ BCR-ABL1 ,[4][4],[5][5] with

This study describes a phytoplasmal disease occurring in Petunia leaves grown in the glasshouse of the National Horticultural Research Institute, Suwon, Korea. Abnormal growth like flattened stem with flower malformation or phyllody was observed from the plant. The DNA extracted from the diseased leaves was amplified using a universal primer pair of P1/P6 derived from the conserved 16S rRNA gene of Mollicutes giving the expected polymerase chain reaction(PCR) product of 1.5 kb. In the nested PCR assays, the expected DNA fragment of 1.1 kb was amplified with the specific primer pair R16F1/R16R1 that was designed on the basis of aster yellows(AY) phytoplasma 16S rDNA sequences. The 1.1 kb PCR products were cloned and nucleotide sequences were determined, and the sequences of the cloned 168 rRNA gene were deposited in the GenBank database under the accession no. of EU267779. Analysis of the homology percent of the 168 rDNA of PFS-K showed the closest relationship with Hydrangea phyllody phytoplasma(AY265215), Brassica napus phytoplasma(EU123466) and AY phytoplasma CHRY(AY180956). Phytoplasma isolated from the diseased Petunia was designated as Petunia flat stem phytoplasma Korean isolate(PFS-K) in this study. Flattened stem occurring in Petunia was confirmed as infection of AY group of phytoplasma by determination of 16S rRNA gene sequences of phytoplasma and microscopic observation of phytoplasma bodies. This is the first report on the phytoplasmal disease in Petunia in Korea.

T-cell large granular lymphocytic (T-LGL) leukemia is characterized by cytopenia and clonal proliferation of large granular lymphocytes. We identified 26 patients with T-LGL leukemia seen at our institution over a period of 8 years. The majority of the patients were asymptomatic at diagnosis. Nine patients were treated with cyclosporine; one achieved a complete remission, and four had a hematological response. Other treatment modalities included single agent alemtuzumab, alemtuzumab combined with pentostatin, fludarabine, and combination of fludarabine and cyclophosphamide. Significant responses were not seen with any of these treatment regimens. We conclude that cyclosporine therapy may be beneficial for T-LGL leukemia patients. New treatment modalities are needed for these patients.

In 2003 typical phytoplasma symptoms of witches` broom and flower malformation were observed on statice (Limonium sinuatum) plants grown at commercial greenhouses in Busan, South Korea. The DNA extracted from the infected leaves was amplified using universal primer pair of Pl/P6 derived from conserved 16S rRNA gene of Mollicutes giving the expected Polymerase chain reaction (PCR) product of 1.5 kb. In the nested PCR assays, the expected DNA fragment of 1.1 kb was amplified with the specific primer pair 16Fl/Rl that was designed on the basis of aster yellows (AY) phytoplasma 16S rDNA sequences. The 1.1 kb PCR products were cloned and nucleotide sequences were determined. The sequences were identical to that of Onion yellows OY phytoplasma (GenBank accession no. D12569) isolated from Onion in Japan. Electron microscopy of thin sections of leaf veins showed phytoplasma bodies in the phloem. Statice witches` broom symptom occurred on statice in commercial greenhouses in Korea was confirmed as infection of AY phytoplasma by transmission electron microscopy observation, and by determination of 16S rRNA gene sequences of phytoplasma.

Blast phase (BP) in chronic myelogenous leukemia (CML) frequently is accompanied by cytogenetic abnormalities in addition to t(9;22)(q34;q11.2). We describe 5 patients with CML in blast phase (CML-BP) in which t(9;22) and inv(16)(p13q22) were identified by conventional cytogenetics, with confirmation of BCR/ABL and CBFβ/MYH11 by fluorescence in situ hybridization. The morphologic findings at the time of BP resembled de novo acute myeloid leukemia (AML) carrying inv(16)(p13q22), with abnormal eosinophils in the bone marrow and monocytosis in the peripheral blood in all cases. In 1 patient, inv(16)(p13q22) and abnormal eosinophils were detected in the bone marrow 2 months before CML-BP. The clinical course of these patients was similar to patients with CML-BP without evidence of inv(16)(p13q22). These cases illustrate that inv(16)(p13q22) is a form of cytogenetic evolution that rarely occurs in patients with CML at the time of BP. In this setting, unlike de novo AML, inv(16)(p13q22) in CML-BP is not associated with a favorable prognosis.

Intracranial hemorrhage (ICH) is a common complication in acute myeloid leukemia (AML) patients with an incidence rate of 6.3% [1]. Bleeding disorders related to disseminated intravascular coagulation (DIC) are common complications in AML cases [2]. Recombinant activated Factor VII (rFVIIa [NovoSeven®]) is approved for the treatment of bleeding complications with FVIII or FIX inhibitors in patients with congenital FVII deficiency. Use of rFVIIa for the treatment of acute hemorrhage in patients without hemophilia has been successful [3,4]. Herein, we describe the successful use of rFVIIa in a patient with acute ICH in the setting of newly diagnosed AML.

Karyotypic studies of bone marrow were conducted in 79 previously untreated patients with multiple myeloma who received a standard programme of chemotherapy. An abnormal karyotype was observed in 46% of patients, virtually all showing multiple abnormalities consistent with a long period of preclinical clonal evolution. Patients with an abnormal pattern showed various aberrations with hyperdiploidy in 64%, pseudodiploidy in 5% and hypodiploidy in 31%. The number of chromosomes affected ranged from two to 19 (median 10), with at least one trisomy in 83%, one monosomy in 75%, and one translocation in 42% of patients. Lymphoma-like karyotypes were present in 17% of patients with an abnormality but were not associated with atypical clinical features, such as an extramedullary mass, leukaemia, or increased serum lactate dehydrogenase. Monosomy or deletion of chromosome 13 was present in 47% of patients with an abnormal pattern, who lived for a shorter duration (median 10 months) than patients with other abnormalities (median 34 months) or with diploidy (median 35 months). The cause of the short survival of patients with monosomy or deletion of chromosome 13 was not clear, but further studies on the relationship with specific oncogenes are indicated.

The growth stimulatory effects of interleukin-3 (IL-3) on normal hematopoietic progenitor cells are well established, and clinical trials using IL-3 after bone marrow transplantation for various malignancies including lymphomas are frequently conducted. Although the IL-3 receptor is expressed on the surfaces of follicular small cleaved- cell lymphoma (FSCCL) cells, the in vivo effects of IL-3 on FSCCL have not been studied previously. Because our preclinical data suggested that IL-3 may have dose-dependent inhibitory effects on FSCCL cells in vitro, we treated eight FSCCL patients with high-dose IL-3 in an outpatient setting. Each patient received 1 mg/m2 of IL-3 subcutaneously daily for 14 days followed by 7 days without IL-3. After three courses (9 weeks), the patients were evaluated for clinical responses. One patient had a minor response, and four had no responses. Three patients who had progressive disease before IL-3 treatment continued to have progressive disease. In two patients with bone marrow involvement with lymphoma, IL-3 had no effect on FSCCL cells. One patient with peripheral blood involvement with FSCCL cells that expressed IL-3 receptors had temporary growth arrest of the circulating malignant cells. IL-3 significantly increased the absolute neutrophil count in seven patients (87%) but had little effect on the number of normal circulating B cells. There was an increase in the number of circulating natural killer cells and CD8+ cells in four patients. Treatment was very well tolerated; no life-threatening toxicities were observed. The most common toxicities were injected conjunctivae (100%), fever (100%), fatigue (87%), and skin rash (75%). Most of the side effects subsided with the continued use of IL-3. These preliminary results suggest that high-dose IL-3 does not stimulate the growth of FSCCL cells in vivo and, in some instances, may cause growth inhibition.

7019Background: Despite the development of new MYC-targeted drugs, few studies have assessed MYC protein expression in acute myeloid leukemia (AML). We assessed MYC expression by immunohistochemist...

A clonal myeloproliferative neoplasm (MPN) of the hematopoietic stem cell, polycythemia vera (PV) involves increased red blood cell production, elevated red blood cell mass and variable increases i...

Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 × 109/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

Blast phase (BP) in chronic myelogenous leukemia (CML) frequently is accompanied by cytogenetic abnormalities in addition to t(9;22)(q34;q11.2). We describe 5 patients with CML in blast phase (CML-BP) in which t(9;22) and inv(16)(p13q22) were identified by conventional cytogenetics, with confirmation of BCR-ABL and CBFss-MYH11 by fluorescence in situ hybridization. The morphologic findings at the time of BP resembled de novo acute myeloid leukemia (AML) carrying inv(16)(p13q22), with abnormal eosinophils in the bone marrow and monocytosis in the peripheral blood in all cases. In 1 patient, inv(16)(p13q22) and abnormal eosinophils were detected in the bone marrow 2 months before CML-BP. The clinical course of these patients was similar to patients with CML-BP without evidence of inv(16)(p13q22). These cases illustrate that inv(16)(p13q22) is a form of cytogenetic evolution that rarely occurs in patients with CML at the time of BP. In this setting, unlike de novo AML, inv(16)(p13q22) in CML-BP is not associated with a favorable prognosis.

BACKGROUND CD23 antigen is a cell surface protein considered important in the differentiation of chronic lymphocytic leukemia (CLL) from other lymphoid leukemias. METHODS To better clarify CD23 role as a diagnostic tool, the authors retrospectively evaluated clinical and laboratory features of 372 patients who were referred to M.D. Anderson Cancer Center with a diagnosis of CLL or B-cell chronic lymphoproliferative disease. RESULTS Most of the patients (91%) were CD19+/CD5+. Only 6% of these CD19+/CD5+ patients were CD23−. Overall, CD23− patients had the worse prognostic features compared with CD23+ cases, including anemia (P = 0.03), massive splenomegaly (P = 0.000), high lactate dehydrogenase (P = 0.007), high β2-microglobulin (P = 0.006), older age (P = 0.001), and male gender (P = 0.02). Surface immunoglobulin expression was moderate/strong in 19 (82%) patients, and FMC-7 was positive in 22 (96%) patients. None of the 13 patients tested for CD10 expressed the antigen. Based on morphology, of the CD23, 16 (70%) were diagnosed with mantle cell leukemia (MCL) was diagnosed in 16 (70%) CD23− patients, 3 (13%) with splenic marginal-zone leukemia, 3 (13%) with prolymphocytic leukemia (PLL) or PLL/CLL, and 1 (4%) with CLL. No cyclin D1 protein expression was noted by Western blot analysis in the one case that showed typical CLL morphology, and this patient did not require therapy. On the whole, the survival rate of CD23− patients was significantly worse than that of patients with CD23+. In contrast, 15 of 32 (49%) CD19+/CD5− patients were CD23−. CD23 negativity in this group was not associated with distinct clinical features or outcome. Eleven (73%) of these patients were classified as having splenic marginal-zone lymphoma and 4 as having follicular lymphoma. CONCLUSIONS These data indicate that CD23 negativity is rare in typical B-cell CLL, and CD23 negativity in patients with CD19+/CD5+ is suggestive of mantle cell leukemia a more aggressive disease with poor response to conventional therapy in which newer chemotherapy regimens such as hyper-CVAD may be more effective. Cancer 2002;94:1721–30. © 2002 American Cancer Society. DOI 10.1002/cncr.10401

7094 Background: MYC, a transcription factor controlling DNA replication, is overexpressed in many cancers, yet rarely investigated in myeloid neoplasms, where its clinical significance is unknown....

We investigated the significance of p210 and p190 molecular abnormalities in 32 adults with Philadelphia chromosome (Ph)-positive acute leukemia. p210 was detected in 15 patients (47%), p190 in 16 (50%), and both in one (3%). p210 was noted in 11 of 24 patients (46%) with acute lymphocytic leukemia, and in four of eight patients (50%) with acute myelogenous or undifferentiated leukemia. Among 29 patients with untreated disease (p210, 14 patients; p190, 15 patients), no significant differences in the two molecularly distinct groups were observed by pretreatment characteristics including age, degree of organomegaly, anemia, leukocytosis, thrombocytopenia, occurrence of karyotypic abnormalities in addition to Ph, or residual diploid metaphases. Complete response (CR) rates were also similar. Although the remission duration tended to be longer with p190 (P = .08), the differences were minor (median duration 29 v 20 weeks) and not paralleled by differences in survival rate. In 10 patients studied by karyotypic analysis in remission, two of four patients with p190 and two of six patients with p210 showed 100% normal metaphases. One of the seven patients (14%) with p210 who achieved CR manifested a morphologic picture of second chronic-phase chronic myelogenous leukemia lasting for 1 month. We conclude that the molecular studies in Ph-positive acute leukemia are not associated with significantly different clinico- laboratory, karyotypic, or prognostic implications.