Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.
Adolescent ; Adult ; Aged ; Anemia, Aplastic ; Bone Marrow ; Child ; Chromosomes, Human, Pair 8 ; Clonal Evolution ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Trisomy ; Young Adult

Clonal Evolution ; Humans ; Multiple Myeloma

Clonal Evolution ; Clone Cells ; Humans ; Myelodysplastic Syndromes

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

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

OBJECTIVETo evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).

METHODSThe clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.

RESULTSThe 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.

CONCLUSIONSThe children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.

Adolescent ; Anemia, Aplastic ; drug therapy ; genetics ; immunology ; mortality ; Child ; Child, Preschool ; Chromosome Aberrations ; Clonal Evolution ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Proportional Hazards Models ; Retrospective Studies

BACKGROUND: It is widely known that the prognosis of acute myeloid leukemia (AML) depends on chromosomal abnormalities. The majority of AML patients relapse and experience a dismal disease course despite initial remission. METHODS: We reviewed the medical records and laboratory findings of 55 AML patients who had relapsed between 2004 and 2013 and who had been treated at the Division of Hematology of the Pusan National University Hospital. RESULTS: The event-free survival (EFS) was related to prognostic karyotype classification at the time of diagnosis and relapse (unfavorable vs. favorable or intermediate karyotypes at diagnosis, 8.2 vs. 11.9 mo, P=0.003; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.2 vs. 11.9 mo, P=0.009). The overall survival (OS) was significantly correlated with karyotype classification only at diagnosis (unfavorable vs. favorable or intermediate vs. karyotypes at diagnosis, 8.5 vs. 21.8 mo, P=0.001; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.5 vs. 21.2 mo, P=0.136). A change in karyotype between diagnosis and relapse, which is regarded as a factor of resistance against treatment, was not a significant prognostic factor for OS, EFS, and post-relapse survival (PRS). A Cox proportional hazards model showed that the combined use of fludarabine, cytosine arabinoside, and granulocyte colony-stimulating factor (FLAG) as a salvage regimen, was a significant prognostic factor for OS (hazard ratio=0.399, P=0.010) and the PRS (hazard ratio=0.447, P=0.031). CONCLUSION: The karyotype classification at diagnosis predicts survival including PRS in relapsed AML patients as well as in treatment-naïve patients. We suggest that presently, administration of salvage FLAG could be a better treatment option.
Busan ; Chromosome Aberrations ; Classification ; Clonal Evolution* ; Cytarabine ; Diagnosis ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; Hematology ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; Medical Records ; Prognosis ; Proportional Hazards Models ; Recurrence

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

OBJECTIVETo study the clinical features of patients with refractory cytopenia of childhood (RCC).

METHODSThe clinical data of 1 420 children (0-14 years old) with an initial diagnosis of non-severe aplastic anemia between January 1990 and June 2013 were retrospectively analyzed. Bone marrow cell morphology and histopathology were re-evaluated, and the patients were re-classified using the criteria proposed in the 2008 edition of the World Health Organization classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical outcomes were followed up every 3-6 months.

RESULTSAmong all the 1 420 cases, 152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at diagnosis. The median follow-up period for all patients was 36 months (ranging from 1 to 283 months). The rates of complete response, partial response, and no response to cyclosporine and androgen treatment in RCC patients were 19.0%, 26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year prospective incidence of newly diagnosed karyotype abnormality after the initial diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates were 10.0% and 20.0%, respectively.

CONCLUSIONSRCC shows clinical features similar to adult myelodysplastic syndrome. Children with RCC have a poor prognosis, an increased risk of transformation to leukemia, and a low response rate to cyclosporine treatment.

Adolescent ; Child ; Child, Preschool ; Clonal Evolution ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Myelodysplastic Syndromes ; drug therapy ; mortality ; Pancytopenia ; drug therapy ; mortality ; Prognosis ; Retrospective Studies

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