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Objective: To investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML)., Methods: The karyotypes of 3743 patients with newly-diagnosed de novo AML were analyzed, which had identified 153 cases with MK-AML, for whom the clinical and genetics characteristics were analyzed., Results: There were 2056 patients (54.9%) among all patients. A total of 153 patients fulfilling the criteria for MK-AML were identified, which comprised 93 males and 60 females, with a median age of 54. The median white blood cell count on presentation was 4.4×10 (9)/L. One hundred and forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (≥ 3 chromosomal abnormalities). Although the monosomy could be found with all autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153)., Conclusion: MK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is frequently detected among MK-AML patients. The monosomal karyotype is common among elder patients with AML.

Human leukemia cell lines are powerful tools in the study of leukemogenesis, particularly for rare but recurrent subtypes such as acute myeloid leukemia (AML) with the t(16;21)(p11.2;q22) and FUS-ERG fusion. Four AML cell lines carrying a t(16;21)(p11.2;q22) have been described previously. We report a novel AML cell line, designated JIH-4, for which karyotypic analysis demonstrated a single abnormality, t(16;21)(p11.2;q22). The FUS-ERG fusion transcript was identified by reverse transcriptase polymerase chain reaction (RT-PCR). Neither Epstein-Barr virus nor mycoplasma was detected in JIH-4 cells. The morphology and immunoprofile of JIH-4 cells display typical features of myelogenous lineage, and short tandem-repeat PCR comparison with the donor patient's bone marrow cells confirm the cell line's authenticity. Tumor masses were found in 50% of inoculated mice 83 days after subcutaneous injection with JIH-4 cells. Our results confirm that JIH-4 cells are derived from the donor patient's leukemia cells and support using the JIH-4 cell line as a valuable tool in the study of leukemogenesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

To date, at least 25 translocations involving the NUP98 gene and different partner genes have been reported in the literature. Here, we describe a novel reciprocal t(5;11)(q31;p15) involving NUP98, as revealed by conventional karyotypic analysis using R-banding technique and fluorescence in situ hybridization (FISH) using a BAC RP11-120E20 probe and whole chromosome paint probes for chromosomes 5 and 11 in a 77-year-old woman who was diagnosed as having de novo acute myeloid leukemia. The patient received two courses of intensive combined chemotherapy but did not reach complete remission. She eventually died from the progressive disease, surviving for only 1 month after diagnosis. FISH analysis using WCP5 together with BAC RP11-878F9 or RP11-155N22 demonstrated that the breakpoint of chromosome 5 is located on 5q31. In addition, the EGR1 gene was unexpectedly found to be lost in the FISH study using EGR1 (red)/D5S23, D5S721 (green) dual-color probe. We supposed that the fusion gene created by t(5;11)(q31;p15) consisting of the NUP98 and its partner gene, as well as the loss of the EGR1 gene, may play a cooperative role in leukemogenesis. The partner gene of NUP98 in t(5;11)(q31;p15) is unclear at this time. Further molecular study is required to identify this partner gene in our patient., (2010 Elsevier Inc. All rights reserved.)

Objective: To explore the clinical and laboratory features of 6 cases of acute myeloid leukemia (AML) with t(6;9)(p23;q34)., Methods: Chromosome preparation of bone marrow cells was performed with regular method. R-banding by heating using Giemsa banding technique (RHG) was used for karyotype analysis. The immunoprofile was studied by flow cytometry (FCM) using a panel of monoclonal antibodies. Chromosome painting was performed by using whole chromosome paint probes for chromosomes 6 and 9 in all the 6 cases. The expression of fusion gene DEK/CAN and FLT3-ITD mutation were analyzed by reverse transcription-PCR(RT-PCR)., Results: The t(6;9)(p23;q34) was found in all the 6 cases including 4 cases of M2 and 2 cases of M4. Blast cells were positive for CD13 and CD33 in 6 patients, for HLA-DR in 4 patients, for CD34 and CD117 in 3 cases, for CD38 or CD15 each in 1 case, respectively. A reciprocal translocation between chromosome 6 and 9 was confirmed by chromosome painting technique in the 6 cases. The DEK/CAN fusion gene was found in all the 6 cases, FLT3-ITD mutation was detected in three of them. Follow-up showed that 3 patients died with a survival time of 3 months, 5 months and 6 months, respectively. The other three obtained complete remission and are still alive., Conclusion: The t(6;9)(p23;q34) is a rare recurrent abnormity. AML with t(6;9)(p23;q34) has unique clinical and laboratory features and its prognosis is poor in most cases.

Acute promyelocytic leukemia (APL) is characterized by the presence of a chromosomal rearrangement involving retinoic acid receptor alpha (RARalpha) gene generating the X-RARalpha fusion. We describe here a unique RARalpha gene rearrangement in a patient with M3r subtype of APL. Conventional cytogenetic analysis revealed Y-chromosome loss as the sole karyotypic anomaly. No X-RARalpha fusion was detected by fluorescence in situ hybridization (FISH) using PML/RARalpha dual-color dual-fusion translocation probe set, or RARalpha dual-color break apart rearrangement probe or reverse-transcription polymerase chain reaction (RT-PCR). However, FISH using RARalpha dual-color break apart rearrangement probe showed a deletion of the entire 3'-end of one allele of RARalpha gene. To our knowledge, this is the first documented APL with 3'RARalpha submicroscopic deletion which is not associated with X-RARalpha fusion. The molecular consequences of this anomaly remain to be elucidated.

Objective: To report here a new acute myelocytic leukemia (AML) cell line SH-2 and describe its biological characteristics., Materials and Methods: Mononuclear cells isolated from a patient with AML-M2 subtype were passaged by liquid culture medium. Interleukin-3 and bone marrow stromal cells were used to support cell proliferation at the first 3 months. Various methods, including cytogenetic analysis, fluorescence in situ hybridization (FISH), multiplex FISH (M-FISH), reverse transcriptase polymerase chain reaction (RT-PCR), multiplex RT-PCR, short tandem repeat (STR)-PCR, direct sequencing of DNA, clonogenic assay, and tumorigenicity in nude and severe combined immunodeficient (SCID) mice were employed to identify and characterize SH-2 cell line., Results: SH-2 cells were maintained without cytokine and stromal cells for 3 years. It had no Epstein-Barr virus or mycoplasma contamination. The SH-2 cell line showed typical myelocytic features in morphology and simultaneous strongly expressed myeloid antigens (CD13, 99.6% and CD33, 99.26%) and natural killer (NK)-related antigens (CD56, 99.5% and CD16/56, 99.62%) suggesting that SH-2 is an AML cell line with NK-antigen expression. SH-2 cell line initially showed a karyotype of 45, X, -Y, der(16)t(16;17)(q24;q12), -17, +19. During the passage period, the cells with a hypodiploid karyotype gradually decreased and were replaced by the near-tetraploid cells with a karyotype of 71-105(86), XX, -Y, -Y, der(16)t(16;17)x2, -17, -17, +19, +19. FISH and M-FISH delineated all abnormalities. SH-2 cells had the approximately same morphological, immunophenotypical, and cytogenetic features as the patient's leukemia cells had. STR-PCR provided powerful evidence for the derivation of SH-2 cell line from the patient's leukemia cells. SH-2 cells showed multiple drug resistance (MDR), which may be related to the p53 gene alteration, including the loss of one p53 allele due to the monosomy 17 and a point mutation of CAG to CAT at codon 576 of exon 5 in another p53 allele resulting in the loss of p53 gene function. In addition, SH-2 cell line did not express MDR-related genes, such as MDR1, multidrug resistance-related protein, and lung resistance protein, but expressed apoptosis-related genes, such as Bcl-2, Fas, glutathione S-transferase-pi, and p21, which were also related to the MDR. SH-2 cell line had tumorigenic capacities in nude and SCID mice., Conclusion: Because SH-2 cell line had a clear biology background, it will provide a useful tool for the study of the pathogenesis and treatment strategy of AML with MDR.

Translocations involving 21q22 are commonly observed in both de novo and therapy-related acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). They often result in the disruption of RUNX1 and give rise to fusion genes consisting of RUNX1 and different partner genes, which contribute to leukemogenesis. To date, at least 21 such translocations are known from the literature. Here we report two novel translocations involving the RUNX1 gene: t(1;21)(q12;q22) in a 53-year-old woman with AML-M5b and t(11;21)(q13;q22) in a 65-year-old man with AML-M2. The abnormalities revealed by R-banding karyotypic analysis were confirmed with interphase and metaphase fluorescence in situ hybridization (FISH), chromosome painting, and M-FISH.

Here we report a rare chromosomal translocation, t(12;22)(p13;q11), which was detected in a 53-year-old female patient diagnosed as having minimally differentiated acute myeloid leukemia (AML-M0) according to the French-American-British classification criteria. Chromosome painting analysis with probes for chromosomes 12 and 22 confirmed the result of the conventional cytogenetic analysis. Reverse transcriptase polymerase chain reaction revealed the TEL-MN1 fusion transcript. Interestingly, she presented primary multidrug resistance and did not respond to several kinds of chemotherapy regimens. Moreover, she could not achieve remission after two doses of monotherapy with Mylotarg. Flow cytometry analysis detected high levels of expression of P-glycoprotein, multidrug-resistant-related protein, lung-related protein, and glutathione S-transferase pi in this case at presentation. As far as we know, this is the first report of t(12;22)(p13;q11) translocation involving TEL and MN1 genes in an AML-M0 patient., (Copyright 2007 S. Karger AG, Basel.)

Objective: To study the clinical and cytogenetic characteristics of four patients with myelodysplastic syndrome (MDS) and one with acute myeloid leukemia experiencing t (1;7)., Methods: Five patients seen in our hospital from 1992 to 2001 were diagnosed as MDS and acute myelocytic leukemia (AML) according to the French-American-British (FAB) criteria. Chromosomes were prepared using the direct method as well as 24-hour unstimulated cultures of fresh heparinized bone marrow for each subject, while R-banding was used to analyze karyotypes. Dual-color fluorescence in situ hybridization (FISH) using SpectrumRed and SpectrumGreen directly labeled chromosome 1-specific alpha-satellite DNA probe (red) and chromosome 7- specific alpha-satellite DNA probe (green) was performed for three cases., Results: Of the five patients, three had 1;7 translocation due to a long history of exposure to benzene. In three cases, dual-color FISH resulted in three red signals and two green ones, in which one red signal adjoining one green signal in 27.6%, 84% and 18.5% metaphases, respectively., Conclusions: Exposure to benzene may be the cause for Chinese MDS and AML patients with t (1;7) translocation. The result of dual-color FISH convincingly confirmed that the centromere of the derivative chromosome 7p/1q resulting from 1;7 translocation was made up of centromeres from both chromosomes 1 and 7.