Clonal Evolution ; Humans ; Multiple Myeloma

Clonal Evolution ; Clone Cells ; Humans ; Myelodysplastic Syndromes

BACKGROUND: Accumulation of genetic aberrations in MDS is closely associated with progression to AML. FLT3-ITD is commonly found in AML and less frequently in MDS. FLT3-ITD in MDS is associated with a high risk of transformation to AML. Recently, significant interaction of NPM1 and FLT3-ITD was described in AML. This study was conducted to investigate the incidence and prognostic role of FLT3-ITD and NPM1 mutations (NPM1mt) on paired samples at diagnosis of MDS and AML. METHODS: Patients who were diagnosed as MDS transforming to AML were included. FLT3-ITD was detected by PCR, and NPM1mt was confirmed by direct sequencing after screening for NPM by immunohistochemistry. RESULTS: AML developed in 12.0% (43/357) of MDS patients. FLT3-ITD was detected in none of MDS and 14.7% (5/34) of AML. NPM1mt was detected in 2.4% (1/41) of MDS and 11.6% (5/43) of AML. One patient with type B NPM1mt at MDS transformed to type A NPM1mt at AML. FLT3-ITD positive AML showed a tendency of shorter survival and a significantly longer time to achieve complete remission than FLT3-ITD negative AML (P=0.007). Normal karyotype AML with FLT3-ITD showed shorter overall survival than that group of AML without FLT3-ITD (P=0.017). CONCLUSIONS: MDS patients acquired FLT3-ITD during AML transformation, and FLT3-ITD positive AML, especially that with normal karyotype, predicted a poor outcome. NPM1mt was identified in both MDS and AML. NPM1mt was rarely found in MDS patients, and mostly was acquired after AML transformation. Clonal evolution of NPM1mt subtype was found in one patient during acute transformation.
Clonal Evolution ; Humans ; Incidence ; Karyotype ; Mass Screening ; Polymerase Chain Reaction

No abstract available.
Clonal Evolution* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive*

The ider(22)(q10)t(9;22)(q34;q11.2) is a rare secondary karyotypic aberration of Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) and was associated with disease progression and poor clinical outcomes in most of the previously reported cases. We experienced a case of Ph+ CML with the occurrence of ider(22)(q10)t(9;22)(q34;q11.2) as clonal evolution preceding an hematologic feature of accelerated phase for 3 years. So this chromosomal abnormality was not always correlated with poor prognosis. Relevant literature was reviewed.
Chromosome Aberrations ; Clonal Evolution* ; Disease Progression ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Philadelphia Chromosome ; Prognosis

OBJECTIVETo explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).

METHODSMonosomy 7 (-7) in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with immunosuppressive therapy (IST) and more than 6 months of recombinant human granulocyte colony-stimulating factor (rhuG-CSF) were detected by interphase- fluorescence in situ hybridization (FISH) retrospectively.

RESULTSThere were 5.4% - 7.6% of -7 cells in 11 (13.6%) of 81 patients at diagnosis, the survival and response rate to IST in -7 positive patients did not differ significantly from that in -7 negative patients (P = 0.481, 0.865); -7 cells disappeared after IST in all of the 11 patients including 5 received long-term rhuG-CSF therapy, and none of them evolved to myelodysplastic syndromes/acute myeloid leukemia (MDS/AML) at a median follow-up of 44 months. Serial assessments of -7 clones were performed in 46 patients, none of whom detected -7 clones 3-6 months after IST, but -7 recurrence in 5 patients 12 - 15 months after IST. At a median follow-up of 48 months, FISH identified 6 patients with -7 clones while the conventional cytogenetic analysis (CCA) recognized in 5. Moreover, the first demonstration of -7 by FISH was 3 - 18 months earlier than that by CCA. All of the 6 patients with FISH detected -7 evolved to MDS/AML with -7 and four of them were retrospectively analysed for in samples at -7 diagnosis of AA, but none of them was positive.

CONCLUSIONSMonosomy 7 exists in a part of AA patients, but the preexisting -7 cells seems neither associated with fatality nor evolvation to MDS/AML. rhuG-CSF might facilitate the expansion of -7 clones; It is necessary to monitor -7 in AA, especially when received long-term rhuG-CSF therapy.

The theory of evolution of tumor cell population has been established for nearly 40 years. It was widely accepted for research and clinical anti-tumor treatment. Recently, it was suggested that cancer stem cells are the unit of evolution. Considering recent advances on genesis of tumor and leukemia with ecological and evolutionary views, this article reviews origin and evolution of leukemia stem cells. Over the last few years, clinical and experimental data suggest there are two paths for the origin of leukemia stem cells: from a transformed hematopoietic stem cell or progenitor. The mechanisms of leukemia stem cell formation and clonal evolution were elucidated. Sub-clonal mutations and clonal architectures in leukemia were studied and a mosaic evolution pattern is described. Random evolution or non-inherited mutations of leukemia cells would accelerate the progression of malignant disease. Finally, the mosaic or network mechanism for leukemogenesis is also discussed.
Clonal Evolution ; Disease Progression ; Hematopoietic Stem Cells ; Humans ; Leukemia ; Mutation ; Neoplastic Stem Cells

Almost all patients with multiple myeloma (MM) have chromosomal translocation which can result in genetic variation. There are mainly five types of chromosomal translocations, involving the IGH gene translocation to 11q13 (CCND1), 4p16 (FGFR/MMSET), 16q23 (MAF), 6p21 (CCND3) and 20q11 (MAFB). It is possible that all IGH translocations converge on a common cell cycle signal pathway. Some MM develops through a multistep transformation from monoclonal gammopathy of undetermined significance (MGUS) to smoldering MM (SMM) and eventually to MM and plasma cell leukemia (PCL). Similarly to what Darwin proposed in the mid-19th century-random genetic variation and natural selection in the context of limited resources, MM clonal evolution follow branching and nonlinear mode. The failure of MM treatment is usually related with the minimal subclone which is hardly found at newlydiagnosed.
Clonal Evolution ; Cyclin D1 ; Genes, Immunoglobulin Heavy Chain ; Humans ; Multiple Myeloma ; genetics ; Translocation, Genetic

BACKGROUND: Approximately two thirds of acute myeloid leukemia(AML) have recognizable clonal chromosome abnormalities. We have performed the cytogenetic monitoring of 35 de novo AML to follow the karyotype changes at diagnosis, in remission, and in first relapse. METHODS: The study is based on 35 cases of AML seen between January 1, 1996 and June 30, 1999. They were subdivided in accordance with the FAB classification and treatment response was evaluated by the National Cancer Institute(NCI)-sponsored workshop criteria. Chromosome studies were done with standard 24-48 hour methotrexate synchronization. RESULTS: The frequency of FAB M0, M1, M2, M3, M4, M5, and M6 was 1, 5, 18, 6, 3, 1, and 1, respectively. Clonal chromosome abnormalities were detected in 25 of 35(71%) in the decreasing order of t(8;21), t(15;17), +8, del(9q), etc. Thirty-one(89%) entered complete hematologic remission and 4(11%) represented partial remission. All 31 cases of complete remission had normal karyotypes. Three partial remission patients having both normal and abnormal metaphases at diagnosis and first follow-up had only normal cells after reinduction, however, in 1 case of induction failure, only abnormal metaphases persisted. In 5 of 7 relapses, karyotypes at diagnosis and relapse were identical. Two cases underwent a normal-to-abnormal change and clonal evolution, respectively. CONCLUSIONS: In this study the karyotypes were normal during complete remission, and in relapse the original aberrations returned sometimes with newly acquired clonal abnormalities. Therefore, cytogenetic study yields basic important information for understanding of cancer genetic mechanisms and molecular biologic analysis.
Chromosome Aberrations* ; Classification ; Clonal Evolution ; Cytogenetics ; Diagnosis* ; Education ; Follow-Up Studies ; Humans ; Karyotype ; Leukemia, Myeloid, Acute* ; Metaphase ; Methotrexate ; Recurrence*

OBJECTIVES: To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression. METHODS: An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported. RESULTS: This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period. CONCLUSION These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.
Blast Crisis ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Clonal Evolution ; Disease Progression ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive