Chronic myeloid leukaemia: Biology and therapy.

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions.

[Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia].

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION: The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

[Deciphering Hypoplastic Myelodysplastic Syndrome and Aplastic Anemia via In-Depth Analysis of Lymphocyte Subsets].

OBJECTIVE: To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM). METHODS: The lymphocyte subsets in hypo-MDS (n=25) and AA (n=33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed. RESULTS: The percentage of CD8+T cells in AA group was significantly higher than that in hypo-MDS group (P=0.001), while the percentage of CD4+ T cells and the CD4+/CD8+ ratio in AA group were obviously lower than those in hypo-MDS group (P=0.015 and 0.001, respectively). Furthermore, the proportion of CD4+ and CD8+ activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group (P=0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8+ naive T (TN) cells in AA patients was remarkably higher (P=0.044). And hypo-MDS patients had declined lymphocyte counts (P=0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients (P=0.019, 0.023, 0.027 and 0.045, respectively). CONCLUSION: In this study it was confirmed that the percentages of CD4+ and CD8+ TA cells, memory Tregs and CD8+ TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.

Peripheral blood inflammatory cytokines are associated with rapid eye movement sleep behavior disorder in Parkinson's disease.

OBJECTIVE: Previous studies have shown the essential role of inflammation in rapid eye movement (REM) sleep behavior disorder (RBD). However, the association of RBD in Parkinson's disease (PD) with peripheral blood inflammatory cytokines is still unknown. We investigated the relationship between inflammatory cytokines and the clinical characteristics of PD patients with RBD. METHODS: A total of 153 PD patients and 36 healthy controls were included in this study, and blood plasma was collected. PD patients were classified as PD with RBD (PD-RBD, n = 60) and PD without RBD (PD-nRBD, n = 93). Inflammatory factor levels were compared among the control, PD-RBD, and PD-nRBD groups. RESULTS: The PD-RBD group had significantly higher C-reactive protein (CRP) levels (P < 0.001), monocytes (P = 0.003), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), whereas this group has lower lymphocytes levels (P < 0.001) and lymphocyte-to-monocyte ratio (LMR) (P < 0.001) than the PD-nRBD group. Univariate and multivariate logistic regression analysis indicated that LMR (P < 0.0001 odds ratio [OR] = 0.424) was a protective factor, whereas CRP (P < 0.001 OR = 2.326) was a risk factor for the PD-RBD group. PD-RBD patients had lower Montreal Cognitive Assessment (Beijing version) (MoCA) (P < 0.001) and Mini-Mental State Examination (MMSE) (P = 0.039) scores than PD-nRBD patients. CONCLUSIONS: Significant differences were found in inflammation levels between PD-RBD and PD-nRBD, suggesting that inflammatory factors are associated with the pathogenesis of RBD in PD patients. Thus, CRP and LMR levels may serve as biomarkers and predict the prognosis of PD patients with RBD.

Cognition and transcranial sonography in Parkinson's disease patients with or without orthostatic hypotension.

BACKGROUND: Orthostatic hypotension (OH) is a common nonmotor symptom in patients with Parkinson's disease (PD), with an incidence ranging from 14% to 54%. AIMS: This study explored changes in cognition and transcranial sonography (TCS) findings in patients with PD and OH. METHODS: We enrolled PD patients who visited the outpatient or inpatient department from 2017 to 2020. Blood pressure was measured in different positions, and demographic data were collected. Motor and nonmotor symptoms were evaluated using standard scales. A subset of 107 patients underwent TCS. RESULTS: We enrolled 66 PD-OH patients and 92 PD-no orthostatic hypotension (NOH) patients. There were no significant differences in gender, age, disease duration, or Hoehn and Yahr stage between groups. Binary logistic regression revealed age as an independent risk factor for OH in PD patients. There were statistically significant group differences in visuospatial and executive function and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores (p < .05). Among PD-OH patients, there was a statistically significant difference in UPDRS II and III scores between patients with or without clinical symptoms (p < .05). The substantia nigra (SN) area was significantly larger in PD-NOH patients (0.45 ± 0.18 cm2 ) than PD-OH patients (0.34 ± 0.16 cm2 ) (p < .05). CONCLUSIONS: PD-OH patients had poorer visuospatial and executive function and lower UPDRS I and II scores compared with PD-NOH patients. Within the PD-OH group, there was no significant difference in cognition between patients with or without clinical symptoms. The difference in the SN area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome.

[Differential Expression Profiles of MicroRNAs between de novo and Complete Response Severe Aplastic Anemia].

OBJECTIVE: To detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs. METHODS: The expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray. RESULTS: Totally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules. CONCLUSION: Some miRNA may be involved in the pathogenesis of SAA.

[Long-term Follow-up of Patients with Hepatitis-Associated Aplastic Anemia].

OBJECTIVE: To explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA). METHODS: the clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed. RESULTS: HAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19+ B cells proportion (P=0.046) and more obvious imbalance of CD4+/CD8+ ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001). CONCLUSION: HAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

[Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with Myeloproliferative Neoplasm].

OBJECTIVE: To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN). METHODS: Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene. RESULTS: The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA)6TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease. CONCLUSION: It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.

Clinical Analysis of 70 Adult Patients with Paroxysmal Nocturnal Hemoglobinuria.

OBJECTIVE: To investigate the clinical characteristics of Chinese patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: The clinical data of 70 adult PNH cases in our hospital from January 2000 to December 2009 were analyzed retrospectively, and the clinical manifestation, laboratory examination, treatment, complications and prognostic factors influencing survival rate were assessed. RESULTS: The nosopoietic median age of 70 cases(41 male cases and 29 female cases) was 37 (18-73) years old. The clinical manifestation included fatigue (87.1%), hemogolobinuria (44.3%), infection (22.9%), bleeding (37.1%), and abdominal pain (2.9%). FHb (free hemoglobin) in 56 patients (80%) was <50 mg/L. Hp (haptoglobin) in 54 patients (77.1%) was <0.5 g/L, and LDH in 49 patients (70.0%) was <220 U/L. The overall 10 year-survival rate after diagnosis was 72.2% estimated by Kaplan-Meier. The complications in this study were as follow: recurrent abdominal pain crisis (2.9%), infections (30.0%), thrombotic events (8.6%), evolution to MDS/AML (5.7%), calculus (11.4%) and death (17.1%). Both univariate and multivariate analyses identified risk factors affecting survival, including development of thrombotic events, progression to myelodysplastic syndrome or acute myelogenous leukemia (MDS/AML) and recurrent infections. CONCLUSION: This larger number of cases for the first time allowed us to carry out a detailed analysis of prognostic factors for this rare disease. Evaluation of PNH prognostic factors may provide a basis to assess the current and future therapies of this disease.

[Study on abnormal iron metabolism and iron overload in patients with aplastic anemia].

OBJECTIVE: To investigate the abnormalities of iron metabolism, the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA). METHODS: A cross-sectional study was conducted on 520 newly diagnosed AA patients. RESULTS: Iron overload was observed in 66(13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections(19/86, 22%)than those without infections (47/434, 11%, P<0.01), but also in patients with hepatitis associated AA(HAAA) (6/22, 19%) than the idiopathic cases (60/488, 12%, P>0.05). Excluded the patients with infections and/or HAAA, 43 of 405(11%)cases had iron overload, including 14 of 248(6%) cases without history of blood transfusion and 29 of 157 patients (18%, P<0.01) with transfusion. In univariate analysis, higher levels of serum ferritin (SF), serum iron (SI) and transferrin saturation (TS) were mainly observed in adult male patients with severe AA (SAA) and significantly upward with increasing blood transfusion (P<0.01). No differences of soluble transferrin receptor (sTfR) were observed between adults and children, males and females, hepatitis and idiopathic AA. However, patients with infections had significantly lower level of sTfR (0.50 mg/L) than cases without infections (0.79 mg/L, P<0.01). The level of sTfR in SAA patients (0.70 mg/L) was only half of that in non-SAA (NSAA) (1.36 mg/L, P<0.01). Patients with increasing blood transfusion had significantly downward levels of sTfR (P<0.01). In multivariate analysis, more than 8 U blood transfusion (OR=10.52, P<0.01), adults (OR=3.48, P<0.01), males (OR=3.32, P<0.01) and infections (OR=2.09, P<0.01) were independent risk factors. CONCLUSION: AA patients had higher iron burden and were high-risk populations occurring iron overload. The iron overload occurred in 18% of patients with blood transfusion and in 6% of patients without transfusion.

[The clinical study of myelodysplastic syndromes with PNH clones].

OBJECTIVE: To analyze the clinical characteristics and risk factors on responses and survival of myelodysplastic syndromes (MDS) patients with paroxysmal nocturnal hemoglobinuria (PNH) clones. METHODS: The clinical data of 31 MDS cases with PNH clones from October 2004 to June 2012 were retrospectively analyzed to reveal the influence of PNH clone size on responses and survival. RESULTS: ①The chromosome karyotypes were analyzed in all patients, 23 patients with normal karyotype, 7 patients with abnormal karyotype [including 3 patients with +8, 2 -Y, 1 del(7q) and 1 Xp+] and 1 patient with no mitosis. 1 patient belonged to low-risk, 27 intermediate-1 risk, 2 intermediate-2 risk and 1 high-risk groups, respectively, according to IPSS. There were significantly statistical differences between responders and nonresponders in terms of infection, ANC, Reticulocyte count and IPSS (P values were 0.049, 0.006, 0.031 and 0.043, respectively). ②The overall responsive rate was 67.7%, no patients progressed to acute leukemia (AL) during median follow-up of 19 months after immunosuppressive therapy (IST). The 3-year and 5-year overall survival rates were 82.7% and 55.1%,respectively. ③According to univariate analysis,age, infection and ANC had significant influence on survival (P values were 0.050, 0.031 and 0.026, respectively). ④The PNH clone size had no significant influence on survival through univariate and COX analyses (P=0.393). CONCLUSION: MDS patients with PNH clone had less cytogenetic abnormalities, higher probability of response to IST and lower probability of progression to AL; Furthermore, the PNH clone size had no significant influence on response and survival.

[A long-term follow up study on 345 severe aplastic anemia patients treated with antithymocyte globulin/lymphoglobulin].

OBJECTIVE: To assess the short term curative efficacy and long-term survival outcomes of severe aplastic anemia patients following antithymocyte globulin/lymphoglobulin (ATG/ALG) with or without cyclosporine (CsA). METHODS: A total of 345 cases hospitalized in our hospital between December 1982 and June 2011 were enrolled into this study. We assessed the response rates 3 and 6 months after ATG/ALG, and estimated the overall survival (OS) by Kaplan-Meier method for this cohort of patients. RESULTS: The cohort of 345 patients was routinely followed-up with a median follow-up of 44.0 (range, 0.5 - 244.0) months. The response rates at 3 and 6 months were 29.9% and 45.4%, respectively. The differences in response rates at both 3 (39.2% vs 19.6%, P < 0.01) and 6 months (55.6% vs 34.0%, P < 0.01) between 184 non-severe aplastic anemia (mSAA) and 161 very severe aplastic anemia (VSAA) were statistically significant. The response rates among the different ATG preparations were comparative; but 3-(10.6%) and 6-month (25.5%) responses produced by rATG-Fresenius were significantly inferior to those by rATG-Sangstat (36.6% and 56.6%, respectively) (all P < 0.01). The 5-year OS was 61.7% (95%CI 55.4% - 68.0%) for the entire cohort of patients, and 5-year OS for mSAA patients \[71.0% (95%CI 62.9% - 79.1%)\] was superior to that of VSAA patients \[50.4% (95%CI 40.1% - 60.7%), P < 0.01\]; but for the patients treated from 2007, the difference of OS in the last 5 years between VSAA and mSAA was not significant \[ 73.7% (95%CI 52.2% - 95.2%) vs 89.7% (95%CI 79.5% - 99.9%); P = 0.24\]. Our study also confirmed the superiority of ATG/ALG + CsA regimen \[64.8% (95%CI 57.9% - 71.7%)\] over ATG/ALG alone \[32.6% (95%CI 15.7% - 49.5%)\] with regard to 5-year OS (P < 0.01); but the addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to ATG/ALG had no benefit in terms of OS. rATG-S produced significantly better 5-year OS \[66.1% (95%CI 55.8% - 76.4%)\] than rATG-F \[46.6% (95%CI 35.9% - 57.3%); P < 0.01\]. CONCLUSIONS: (1) The outcome of mSAA was superior to that of VSAA, but the latter was markedly improved in the last 5 years; (2) rATG-F was inferior to rATG-S with regard to 5-year OS; (3) Immunosuppressive treatment with ATG/ALG plus CsA was more effective than ATG/ALG alone; (4) The addition of rhG-CSF to ATG/ALG had no benefit in terms of OS.

[The clinical significance of evolution of paroxysmal nocturnal haemoglobinuria clones in aplastic anemia patients].

OBJECTIVE: To explore the clinical significance of evolution of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) patients. METHODS: The positive rate of PNH clones in 678 AA cases at first diagnosis from January 2002 to December 2009 were analyzed, and to compare the response rate and overall survival (OS) between AA patients with or without PNH clones. All patients were sequentially followed-up to assess the incidence rate and risk factors for AA evolving to overt PNH. RESULTS: (1) Of 119/678 (17.6%) AA patients at initial diagnosis presented with PNH clones,the positive rates of PNH clones among non-severe AA (NSAA), severe AA (SAA) and very severe AA (VSAA) were 16.7% (37/ 222), 17.3% (45/260) and 18.9% (37/196), respectively. There was no statistical difference among the three groups. (Chi2 = 0.369; P = 0.832); (2) 678 newly diagnosed AA cases were divided into 5 subgroups according to PNH clones, severity of disease and treatment regimens. There was no statistical difference among the five subgroups regarding 6m-response rate (RR) and OS. (3) Serial follow-up revealed that persistent PNH negative clones were found in 516 (76.1%) cases, and evolved to PNH positive clones after therapy in 43 (6.3%) cases. Persistent PNH positive clones were found in 72 (10.6%) cases, and disappeared the clones after treatment in 47 (6.9%) cases. There was no statistical difference among the four subgroups in terms of the 6m RR (Chi2 = 2.489,P = 0.426) and OS (P = 0.477); (4) 17 out of 678 AA cases (2.5%) evolved to overt PNH and the estimated incidence of evolution to overt PNH was (3.7 +/- 0.9)% at 10 years. The incidences of AA patients with or without PNH clones at initial diagnosis evolved to overt PNH were 3.4% and 2.3%, respectively. There was no statistical difference between the two groups, (Chi2 = 0.111; P = 0.739); and so was found in OS by Kaplan-Meier analysis (P = 0.868). Cox regression model analysis showed that none of the severity of AA, with or without PNH clone at initial diagnosis, treatment regimen and 6m RR was the risk factor for evolution to overt PNH. CONCLUSION: There is no difference between AA patients presented with or without PNH clones at initial diagnosis regarding the RR and prognosis. The appearance of PNH clones in AA is not identified as a risk factor for developing into overt PNH.

[Genetic detection and enzymatic analyses in α-thalassaemia patients with pyrimidine 5' nucleotidase deficiency].

OBJECTIVE: To explore the clinical significance of genetic detection and changes of red cell enzyme activities of pyrimidine 5' nucleotidase (P5'N), pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G-6-PD) in patients with α-thalassaemia (α-thal). METHODS: Three α-thal patients were further processed to gene detection by PCR-trans-dot blot and gap-PCR, and red cell enzymes activities by absorbance at 260 and 280 nm (A) for P5'N and fluorescence spot test for PK and G-6-PD. RESULTS: Red cells in 3 α-thal cases were microcytic hypochromic with obvious augmented target cells and basophilic stippling erythrocytes. Two patients had anemia, splenomegaly, hyperbilirubinemia and augmented LDH. HbH was positively identified by hemoglobin electrophoresis and hemoglobin cellulose acetate membrane electrophoresis; the other patient had no such abnormalities. Genotypes of 3 patients were of (-α(3.7)/--(SEA)), (αα(QS)/--(SEA))and (--(SEA)), respectively. The activity of P5'N (but not for PK and G-6-PD) in red cell reduced. CONCLUSIONS: This is the first documented α-thal with P5'N deficiency. Genetic detection might be clinical significant for the diagnosis and pedigree screening of α-thal.

[Long-term follow-up of malignant clonal evolution in patients with acquired aplastic anemia].

OBJECTIVE: To assess the incidence and risk factors for evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). METHOD: A total of 1003 AA patients hospitalized in our institute hospital between January 1991 and December 2009 enrolled into this study. The incidence and risk factors for AA developing MDS/AML by the Kaplan-Meier method and Cox proportional hazards models, respectively. RESULTS: The median follow-up was 62 (2 - 423) months and the projected 5-year survival rate was (78.0 +/- 1.0)%. Twenty-seven patients evolved to MDS/AML, of whom 11, 6 and 10 were from NSAA, SAA and VSAA subgroups, respectively. The estimated cumulative incidence of MDS/AML transformation for these 1003 patients after diagnosis was (4.5 +/- 1.0)% at 10 year. The incidence of MDS/AML transformation in VSAA subgroup [(12.8 +/- 3.5)%] was significantly higher than in NSAA subgroup [(4.1 +/- 1.9)%] (P < 0.001) and SAA subgroup [(3.5 +/- 1.4)% ] (P = 0.008), but no difference between the latter two subgroups (P = 0.616). Age [RR = 3.527 (95% CI: 1.598 - 7.784), P = 0.002], severity of disease [RR = 5.122 (95% CI: 2.214 - 11.853), P < 0.001], the duration (days) of rhuG-CSF therapy [RR = 10.782 (95% CI: 4.600 - 25.269), P < 0.001] and exposure to ray, chemicals or drugs [RR = 3.401 (95% CI: 1.535 - 7.534), P = 0.003] were risk factors for the transformation in both univariate and multivariate analyses. CONCLUSION: Long-term follow-up is essential to assess the incidence and risk factors for evolutions of acquired AA into MDS/AML, and to administer salvage therapy for transformation in time during follow-up.

[The application of single-cell gel electrophoresis to the diagnosis of fanconi anemia].

OBJECTIVE: To explore the feasibility of single-cell gel electrophoresis (SCGE) as one of lab tests to examine DNA breakage for the diagnosis of Fanconi anemia (FA). Case Record A 4-year-and-10-month old boy presented with cryptorchism, deformities of both thumbs and esotropia of right eye. He developed thrombocytopenia and anemia when he was 3 year- and -2-month old. He was clinically diagnosed as FA. METHODS AND RESULTS: DNA breakage of peripheral white blood cells from the patient and his parents was examined with SCGE. The percentages of cells with chromosome breakage (comet-tail positive cells) were 100%, 90% and 52% for the patient,his father and mother, respectively, while that were only 2% and 5% in two normal same-age children (P <0. 001). The micronucleus-positive lymphocytes was 6.74% in the patient, being also much higher than normal value (0.40%). CONCLUSION: SCGE disclosed DNA breakage in the patient with FA, suggesting that it could be used as a test for determining DNA breakage of FA.

[Karyotypic and IPSS grouping of primary myelodysplastic syndromes patients: a comparison between FAB- and WHO-classification].

OBJECTIVE: To compare the results of cytogenetic and IPSS grouping of primary myelodysplastic syndromes (pMDS) patients classified by FAB- or WHO classification. METHODS: Two hundred and thirty seven cases of pMDS who were previously classified according to FAB criteria were reclassified with WHO classification. A comparison was made between the results of the two classifications. RESULTS: For the detection rates of cytogenetic abnormality and its risks group, there was no difference among the FAB subgroups but the detection rate was different between the WHO refractory cytopenia with multilineage dysplasia (RCMD) and RA subgroups (74.4% and 42.5%, respectively) (P < 0.001). The percentage of good karyotype abnormalities in RA (65.0%) was higher than that in RCMD (24.4%) (P < 0.001), and the percentages of intermediate and poor karyotype abnormalities in RCMD (48.9% and 26.7%, respectively) were higher than that in RA (27.5% and 7.5%, respectively) (P < 0.05). There was a good correlation between the subgroups and IPSS risk groups for both the WHO classification and the FAB classification, but the WHO classification further reflected the differences between RCMD and RA and RAEB-I and RAEB-II subgroups. The percentage of low-risk group in RCMD (1.1%) was lower than that in RA (10.0%) (P < 0.05), and the percentage of high-risk group in RAEB-II (30.5%) was higher than that in RAEB-I(0) (P < 0.001). CONCLUSION: For the correlation between subgroups and cytogenetic abnormalities and IPSS risk groups, the WHO-classification is better than the FAB-classification.