The clinical and experimental analyses of a multiple myeloma patient with derivative der(Y;1) / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of a rare chromosome abnormality der(Y)t(Y;1) in a patient with multiple myeloma (MM).</p><p><b>METHODS</b>The chromosome spread was prepared after 24 h culture of bone marrow. G-banding technique was used to analyze the karyotype. Fluorescence in situ hybridization (FISH) was performed to ascertain the origin of abnormal chromosome detected by conventional karyotypic analysis. Flow cytometry was used to detect the expression of the CD38/CD138/ZAP70. Immunoelectrophore was applied to identify the type of immunoglobulin.</p><p><b>RESULTS</b>A complex pattern of chromosome rearrangement was observed: 92,XXYY[3]/49,X,der(Y)t(Y;1)(q12;q21),t(11;14)(q13;q32),+18,+20,+21[47]/49,X,idem,del(13q22),ace[1]/98,XX,der(Y)t(Y;1) x 2,+18,+18,+20,+20,+21,+21[10]/46,XY[19]. The result was confirmed by metaphase-FISH. The type of immunoglobulin was IgD with the level of 6.24g/L. The CD38/CD138 was positive but ZAP70 was negative.</p><p><b>CONCLUSION</b>Structural abnormality of chromosome Y is rare in blood malignancy. Most of them were described in myelodysplastic syndrome or myeloproliferative disorders. It is the first report of der(Y)t(Y;1) abnormality in multiple myeloma.</p>

Analysis of variant translocation der ins (17; 15) in patient with APL by G-banding technique and interphase fluorescence in situ hybridization / 中国实验血液学杂志

To investigate the biological characteristics of the variant translocation der ins (17;15) in a patient with acute promyelocytic leukemia (APL), the conventional G-banding technique, interphase fluorescence in situ hybridization (int-FISH), RT-PCR, gene scanning, gene sequence and flow cytometry were performed. The results indicated that the variant translocation der ins (17, 15) observed by G banding technique was a rare type, the int-FISH assay by using dual-color pml/raralpha fusion probes confirmed the cytogenetic findings. The detection results of other molecular methods demonstrated the existence of the whole pml/raralpha fusion gene, while this case had insertion variant translocation. This patient got complete remission by using combined chemotherapy, and survives with continuous complete remission during following up for 1 year. In conclusion, the variant translocation der ins (17; 15) is rare type in APL, its incidence is lower, several signal types in detection of int-FISH were observed and the combination chemotherapy for this patient showed more obvious efficacy.

Characteristics of cases with chromosome 3q21q26 aberrations / 中国实验血液学杂志

To investigate the cytogenetic and clinical characteristics of inv(3q) (q21q26) and t(3;3) (q21; q26) aberrations as well as prognosis, cases were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, while G-banding technique was used to perform karyotyping. The results showed that the simple inv(3q) and t(3; 3) aberrations were rare, they commonly combined with other chromosome aberrations such as -7/7q- and t (9; 22). The involved diseases included myelodysplastic syndromes, acute myeloid leukemia and chronic myelogenous leukemia in blast crisis. Out of 24 patients, 2 patients diagnosed with M(5) subtype did not achieve complete remission after multiple chemotherapy; 2 patients received allogenic stem cell transplantation relapsed. It is concluded that 3q21q26 aberration commonly combined with chromosome aberration 7/7q-, for these patients the efficacy of chemical therapy is poor, the efficacy of bone marrow transplant is too poor, these patients with inv(3q) and t(3; 3) aberrations have poor prognosis and short overall survival.

The efficacy of imatinib mesylate for 124 patients with chronic myeloid leukemia in accelerated and blastic phase / 中华血液学杂志

<p><b>OBJECTIVES</b>To evaluate the efficacy and safety of imatinib mesylate (imatinib) for patients with Philadelphia chromosome-positive (Ph+ ) chronic myeloid leukemia (CML) in accelerated and blastic phase.</p><p><b>METHODS</b>Seventy-five Ph+ CML patients in accelerated phase and 49 in blastic phase were treated with 400 mg or 600 mg of imatinib once daily.</p><p><b>RESULTS</b>For patients in accelerated phase, the cumulative hematological response (HR) rate was 93.3%, including complete HR (CHR) rate 85.3%, and returning to chronic phase (RCP) rate 8% in a median follow-up of 23.0 (1.0 -64.0 ) months. Cumulative major cytogenetic response (MCyR) rate was 33.0%, and complete cytogenetic response (CCyR) rate 28.0%. For patients with CCyR, the major molecular response (MMoR) rate was 47.6%. The estimated 4-year progression-free survival (PFS) rate and overall survival (OS) rate were 48.2% and 52.2% in patients with HR, respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 37.3%, 34.6% and 45.3% of all patients, respectively. For patients in blastic phase, the cumulative HR rate was 63.3%, including CHR rate 44.9%, and RCP rate 18.4% in a median follow-up of 4.5 (0.3 -63.0) months. Cumulative MCyR rate and CCyR rate were both 12.2%. For patients with CCyR, the MMoR rate was 33.3%. For patients with HR, the estimated 1-year/2-year PFS and OS rates were 32.8%/15.8% and 46.0%/ 21.0% respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 75.5%, 71.4% and 73.5% of all patients, respectively.</p><p><b>CONCLUSIONS</b>The efficiency of imatinib was decreasing, and severer hematological toxicities increasing with the disease progressing in patients with Ph+ CML. Imatinib improves progression-free survival significantly in most patients in accelerated phase, particularly in those with continuous CCyR or MMoR. The response duration in majority of blastic phase patients is short, and the relapse rate is high.</p>

Cytogenetic study of multiple myeloma / 中国实验血液学杂志

To investigate the cytogenetic characteristics of multiple myeloma and its relationship with clinical prognosis, 68 cases were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotype analysis. The results showed that the detected chromosome aberration rate was 19.1% (13/68). The abnormal clones existed mosaically with normal clones. Numerous aberrations were manifested by aneuploidy, mainly by hyperdiploidy or hypodiploidy. Structural aberrations involved t (11; 14), chromosome 1 and various kinds of marker chromosomes. Cases which had very complex aberrations revealed poor prognosis. It is concluded that chromosome complex aberration is the mainly cytogenetic characteristics of multiple myeloma, and multiple numerous and structural aberrations are involved. Cytogenetic detection should be performed both at diagnosis and at disease progression so as to evaluate prognosis.

Cytogenetic study on eosinophilia / 中国实验血液学杂志

The aim of study was to investigate the importance of chromosome aberration in differential diagnosis of eosinophilia and the chromosomal aberrations involved in patients with clonal eosinophilia. 65 cases of eosinophilia were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotyping. The results showed that out of 65 cases, chromosome 16 inversion was detected in 9 patients suspected as M(4Eo), and among the other 56 cases, 5 were detected with chromosomal aberrations (8.9%). Combining clinical, hematological and cytogenetical data, the 5 patients were diagnosed as acute myeloid leukemia with eosinophilia, chronic eosinophilic leukemia, 8p11 myeloproliferative syndrome, chronic myeloid leukemia in acute phase and acute myeloid leukemia-M(4Eo) respectively. The detected chromosomal aberrations were +14, t (5; 12) (q31; p13), t (8; 9) (p11; q32), t (9; 22) (q34; q11) and inv (16) (p13 q22). In conclusion, cytogenetical detection is very important in differential diagnosis of clonal eosinophilic disorders and chronic eosinophilic leukemia, which is suggested to be done routinely in clinic.

Studies of treatment strategy and prognosis on acute myeloid leukemia with chromosome 8 and 21 translocation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the biological features and the treatment efficacy and prognosis in acute myeloid leukemia subtype M2 (AML-M2) patients with chromosome 8 and 21 translocation.</p><p><b>METHODS</b>By using Cox regression model and Kaplan-Meier analyses, prognostic factors in 54 cases of de novo adult AML with t(8;21) in our institute from 1990 to 2003 were retrospectively analyzed.</p><p><b>RESULT</b>The complete remission (CR) rates were 81.9% for all M2 patients, 82.4% for patients with normal karyotype, 88.5% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], 100.0% for 28 patients with t(8;21) alone and 75.0% for 24 patients with additional chromosome abnormalities (P < 0.01). The actuarial 3 year overall survival(OS) was 26% for M2 patients with normal karyotype, 25% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], in whole t(8;21) group, 46.4% for patients with t(8;21) alone and 0% for patients with additional chromosome abnormalities (P < 0.01). Multivariate analysis of prognostic factors showed that chromosome abnormalities besides t(8;21) was the only factor affecting CR, disease-free survival (DFS) and OS. DFS of allogeneic hematopoietic stem cell transplantation (HSCT) and intermediate-dose cytarabine/high dose cytarabine (IDAC) groups were better than the group received routine dose cytarabine as postremission therapy (P < 0.01).</p><p><b>CONCLUSION</b>AML with t(8;21) is not a single defined AML subset, and patients with additional chromosome abnormalities have a worse prognosis. HSCT and IDAC could improve the outcome. HSCT is the best choice for patients with high risks, especially with additional chromosome abnormalities.</p>

Clinical study of Philadelphia chromosome-positive acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and therapeutic outcome of Ph+ acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Thirty previously untreated cases of Ph+ B-ALL were diagnosed in our institute. The patients were treated with combination chemotherapy of CODP +/- L regimen, Imatinib (400 approximately 600 mg/d) was continuously given to those who couldn't reach CR. Fourteen patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR, while 16 received consolidation of intensive chemotherapy.</p><p><b>RESULTS</b>Thirty (32.6%) of 92 ALL patients were diagnosed as Ph+ ALL, with a median age of 25.5 (14 - 60). Among them Ph+ as the sole anomaly was seen in 16 patients, and Ph+ with additional chromosome abnormalities in 14. Besides the B cell markers, 23 (76.7%) patients had CD34+ and 13 (43.3%) CD13+ and/or CD33+. Nineteen of the Ph+ ALL patients underwent molecular analysis; 13 (68.4%) expressed P190 and 6 (31.6%) P210. Increased WBC (> 30 x 10(9)/L) was found in 22/30 cases while WBC > 100 x 10(9)/L in 9/30 cases. The chemotherapy complete remission rate was 68.8% in patients with only Ph+ versus 28.6% in those with additional chromosome abnormalities. All seven refractory/relapsed patients reached CR with Imatinib therapy. The total complete remission rate was 73.3% in all Ph+ ALL patients. The median remission duration was shorter in patients with additional chromosome than in those with only Ph+ (1 vs 7 months, P < 0.05), and so was the survival period (7 vs 9 months, P > 0.05). The remission duration was significantly longer in patients received allo-HSCT than in those received chemotherapy only (8 vs 0.5 month, P < 0.05), and so was the survival period (12.5 vs 6 months, P < 0.05).</p><p><b>CONCLUSION</b>Additional chromosome abnormalities negatively affect the prognosis and therapeutic effect of Ph+ ALL patients. Imatinib is effective for the induction therapy of Ph+ ALL. The survival period of patients who received allo-HSCT was obviously longer than those who received chemotherapy only.</p>

Clonal evolution of abnormal Philadelphia chromosome-negative cells after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph- CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).</p><p><b>METHODS</b>Bone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase (BP).</p><p><b>RESULTS</b>After a median follow-up of 32 months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses.</p><p><b>CONCLUSION</b>Ph- CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph- CE were in a stable status with no disease progression.</p>

Monitoring bcr/abl mRNA levels in imatinib mesylate treated chronic myeloid leukemia patients by real-time quantitative RT-PCR / 中华血液学杂志

<p><b>OBJECTIVE</b>To quantify bone marrow bcr/abl mRNA levels in imatinib mesylate treated Ph chromosome positive chronic myeloid leukemia (CML) patients.</p><p><b>METHODS</b>Serial monitoring of bcr/abl mRNA levels by real-time quantitative RT-PCR technique (RQ-PCR) was performed in 34 cases (120 samples) of CML treated with imatinib mesylate. All the patients were IFNalpha based treatment failure before enrolled in this study and the percentage of Ph(+) bone marrow cells were over 95%.</p><p><b>RESULTS</b>The sensitivity of RQ-PCR was 10 pg RNA, with both coefficients of interassay and intraassay variation below 5% for standard samples. The median bcr/abl mRNA level of 10 patients' samples pre imatinib treatment was 5.79% with marked variation (0.24%-60.90%). In 72 samples post imatinib treatment, which the rates of Ph(+) cells [Ph(+)%] were between 0 and 94%, the mRNA level well correlated with Ph(+)% (r = 0.82, P < 0.001). The mRNA levels of 7 patients who achieved complete cytogenetic response (CCyR) within 12 months decreased markedly, the levels of 6 analysable patients decreased by 65.9% - 98.8% after 3 months'treatment accordingly. The level further decreased to 0 after achieving CCyR. For 4 patients who achieved major cytogenetic response (Ph(+) cells < 35%) later than 12 months, the mRNA levels decreased slowly. The levels of 3 analysable patients on 3 month therapy decreased by 2.5%, 18.5% and 61.6% compared with that before treatment. Out of 5 patients in chronic phase without cytogenetic response, 1 decreased, 2 increased gradually and 2 had no change. In 4 disease progression patients, the levels increased stepwise.</p><p><b>CONCLUSIONS</b>Serial quantifications of bcr/abl mRNA levels are necessary for imatinib treated patients, and are more informative than a single detection. A sharp decline of bcr/abl mRNA levels after the treatment implies a promise of CCyR.</p>

STI571 used in treating acute myeloid leukemia with Philadelphia chromosome / 中国实验血液学杂志

The objective was to use STI571, a kind of tyrosine kinase inhibitor, to treat acute myeloid leukemia (AML) with Philadelphia chromosome. 2 AML cases with Philadelphia chromosome, were collected to observe effect of STI571. One of them was given STI571 after routine chemotherapy failed to respond to treatment, other case received routine chemotherapy only. Both of them underwent HLA-matched/mismatched sibling hematopoietic stem cell transplantation (HSCT). The results showed that cytogenetic and hematologic CR was acquired in case 1 with STI571 while another one gained hematologic CR by accepting routine chemotherapy. Recovery of hemopoiesis was found at 18 and 11 days after HSCT respectively without serious graft-versus-host-disease. The case 1 has been surviving in disease-free state for 5 months since HSCT. The case 2 died from interstitial pneumonia at 8 months after HSCT. In conclusion, STI571 is one of choice for the treatment of Philadelphia chromosome positive AML.

Characteristics and prognostic factors of acute myeloid leukemia with t (8; 21) (q22; q22) / 中国实验血液学杂志

The translocation t (8; 21) (q22; q22) frequently associated with additional chromosomal aberrations is one of the most recurrent chromosomal abnormalities in AML. Clinically, this type of AML usually shows some specific characteristics and has a good response to chemotherapy with a high remission rate and a relatively long median survival. On the other hand, some reports also showed poor prognosis in AML patients with t (8; 21), and the associated bad-prognosis factors have not been strongly established to date. To investigate this issue and to further identify the related characteristics of t (8; 21) AML in China, 75 Chinese AML patients with t (8; 21) were retrospectively analyzed. They comprised 68 cases of M(2), five of M(4) and two of M(5) according to FAB classification. The results indicated that Auer rods were observed in 39 patients (52%) and marrow eosinophilia was detected in only 5 patients (6.7%). These patients showed high level of HLA-DR and CD34 expression, while CD19 was detected in only 13 patients (20.9%). Cytogenetically, 62.5% cases had additional chromosomal abnormalities, and the main associated recurrent additional abnormalities were loss of a sex chromosome (LOS), trisomy 4, del (9q) and trisomy 8. After conventional induction therapy, 62 patients attained complete remission (CR) resulting in the CR rate 82.7%. With a follow-up of 1 to 96 months, 19 cases relapsed at a median time of 10.5 months (range 3 to 42 months). The median overall survival was 20 months, and the estimated 5-year overall survival (OS) rate was 32.3%. In multivariate analyses of prognostic factors, karyotype, extramedullary leukemia, age and post-remission therapy were of prognostic value for OS. Patients with additional chromosomal anomalies had shorter survival compared to those with t (8; 21) only (P = 0.019), no matter which kind of additional karyotype it was. Extramedullary leukemia was an adverse prognostic factor (P = 0.012). Patients aged 15 years or less had a longer survival than those aged more than 15 years (P = 0.045). Patients accepted HSCT in post-remission therapy had better outcome compared to those with chemotherapy only. It is concluded that Chinese AML patients with t (8; 21) had some different characteristics as compared with patients from other countries, a relatively poor outcome was observed in our patients, especially in those with extramedullary leukemia or additional chromosomal abnormalities. HSCT should be recommended to t (8; 21) AML in China, especially to those with adverse prognostic factors.

Cytogenetic and clinical study of Philadelphia chromosome positive adult acute leukemia / 中国实验血液学杂志

To explore the cytogenetics and related clinical characteristics of adult acute leukemia with Philadelphia chromosome positive (Ph(+)AL), MIC classification by morphology, immunology and cytogenetics was used to retrospectively study 79 patients with Ph(+)AL hospitalized in the Institute of Hematology, People Hospital in Beijing from October 1991 to September 2003. The results showed that 6.9% cases were diagnosed as Ph(+)AL and classified into three subtypes: acute lymphoblastic leukemia (Ph(+)ALL) in 56 patients (18%), acute myeloid leukemia (Ph(+)AML) in 10 patients (1.2%) and mixed acute leukemia (Ph(+)MAL) in 13 patients. B-cell antigen expression was found in 52 out of 56 patients with Ph(+)ALL. 54.4% (43/79) patients had additional chromosome abnormalities including chromosome 7, double Ph and plus 8, etc. Complete remission (CR) rate of Ph(+)ALL and Ph(+)MAL was 57.0%, none of Ph(+)AML achieved CR. Median overall survival of Ph(+)ALL, Ph(+)MAL and Ph(+)AML were 10, 10 and 2.5 months respectively. It is concluded that Ph(+)AL has highly heterogeneity involving various differentiated stages of immature leukemic cells. Since the poor prognosis associated with this kind of AL, early diagnosis with MIC classification is a prerequisite to take more effective conditioning regimen and prospectively consideration of allogeneic stem cell transplantation to improve prognosis.

Two Ph chromosome positive chronic myelogenous leukemia patients with rare bcr/abl fusion gene / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the unusual bcr/abl fusion gene structures of two Ph chromosome positive chronic myelogenous leukemia (CML) patients in chronic phase (CP).</p><p><b>METHODS</b>By using general M- and micro -bcr/abl specific primers respectively, bcr/abl fusion transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR). The RT-PCR products sequencing was performed, the DNA sequences were analyzed in Genebank and the bcr and abl sequences at the fusion site were identified. DNA was amplified by PCR using a set of primers designed according to the sequencing result of RT-PCR products.</p><p><b>RESULTS</b>Two patients showed typical manifestations of CML-CP. Their RT-PCR products were different from usual M- or micro -type; one was longer than M-bcr/abl but shorter than micro -bcr/abl, the other one was shorter than M-bcr/abl. The RT-PCR products sequencing showed that both products contained bcr and abl gene sequences. The first patient's bcr gene was broken within exon 18, and fused to abl gene exon 2(a2), and a 40 bp of partial abl intron 1b fragment was inserted between them, resulting in a novel in-frame bcr/abl fusion transcript-e18-int-a2 which has not been reported in the literature so far. In the second patient, deletion of abl exon2(a2) led to exon 13(b2) of bcr gene fusing with abl exon 3(a3).</p><p><b>CONCLUSION</b>Uncommon bcr/abl fusion gene may occur in typical Ph(+) CML patient.</p>

Clinical significance of continuous karyotyping in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between evolution of karyotype and clinical progress in myelodysplastic syndromes (MDS) and estimate the clinical outcomes of high risk patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Continuous karyotyping were performed using short-term culture of bone marrow cells and G-banding technique to follow up 41 cases of MDS patients.</p><p><b>RESULTS</b>Karyotype analysis showed that 24 cases (58.5%) had clonal karyotypic abnormalities. In a median follow up of 34 months (7 approximately 72 months), 6 cases had karyotype evolution in 12 cases with clinical deterioration, while only one had karyotype evolution in 18 cases without clinical progression. The involved chromosomes included No. 2, 4, 7, 8, 10, 11, 17 and 21. Six out of 7 patients who received allo-HSCT attained complete remission and their abnormal karyotypes returned to normal. Four patients with clinical remission after therapy attained cytogenetic remission too.</p><p><b>CONCLUSION</b>Karyotype evolution showed a strong relationship with clinical progress in MDS patients, and indicated a very poor prognosis. Patients with clinical progress had much higher incidence of clonal evolution than those with relatively stable clinical course. Allo-HSCT should be considered the first choice of therapy for MDS patients with clonal karyotypic abnormalities.</p>

Study on karyotype of 306 cases of myelodysplastic syndrome / 中国实验血液学杂志

The purpose of this study was to explore the significance of abnormal karyotype in diagnosis and prognosis estimation of myelodysplastic syndrome (MDS). Chromosome analysis were performed in 306 cases of MDS using the short-term culture of bone marrow cell and G-banding technique, and in partial cases FISH technique was used for this analysis. 93 out of 306 cases were followed up. The results showed that 144 cases (47.1%) had clonal chromosome aberrations. The most common chromosomal aberrations included +8, translocation, complex or high complex karyotype, -7/7q-, 20q-/-20, trisomy 1 or partial trisomy 1, +11/+11q-, -9/9q-, +9/9q+, -Y, dup(1q), +21. The rate of abnormal karyotype in refractory anemia with erythroblasts (RAEB) and refractory anemia with erythroblasts-transformation (RAEBT) were much higher than in refractory anemia (RA) and refractory anemia with sideroblasts (RAS) (P < 0.05). The rate of abnormal karyotype among those cases with mutagen contact history were higher than those in cases without mutagen contact history. The patients with abnormal karyotype had a mean survival time much shorter than patients with normal karyotype (P < 0.005) and had a higher risk transforming into acute leukemia (P < 0.05). The worst outcome was observed in those patients with a complex or high complex karyotype, -7/7q- and trisomy 11. In conclusion, MDS is highly heterogeneous disorders and karyotype analysis is helpful for its diagnosis, treatment selection and prognosis estimation.

Cytogenetic and clinical characteristics in 31 cases of blood diseases with aberrations at short arm of chromosome 12 / 中国实验血液学杂志

To investigate the cytogenetic and clinical characteristics in patients with abnormalities at the short arm of chromosome 12, chromosome specimens were prepared by 24-hour culture of bone marrow cells and undergone karyotype analysis by G-banding technique. The results showed that aberration at the short arm of chromosome 12 were detected in 16 cases with 12p balanced translocation, in 10 cases with 12p deletion, 6 cases with 12p addition, and in 1 case with inversion 12. By complex karyotype classification, 12p translocation included 6 simple aberrations, 6 complex aberrations, and 4 highly complex aberrations; while 12p deletion were mainly composed of highly complexity of aberration. Patients consisted of acute leukemia, myelodysplastic syndrome, chronic myelogenous leukemia and so on. Clinical follow-up data were available in 14 patients, in which 8 cases of acute leukemia were treated with conventional chemotherapy only. Three of them attained complete remission, and the median survival time in 8 patients was 5.5 months. In conclusion, the aberrations at short arm of chromosome 12 were involved in a broad spectrum of haematological malignancies, and the karyotypes showed most complexity of aberration with low remission rate and short survival in clinic.

Study on relationship between different bcr/abl fusion transcripts and clinical manifestations in chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between three types of bcr/abl fusion transcripts and clinical manifestation in chronic myeloid leukemia (CML).</p><p><b>METHOD</b>M-, m- and micro -bcr/abl fusion transcripts were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 537 fresh bone marrow samples of patients suspected CML clinically.</p><p><b>RESULTS</b>Of 573 patients, 479 expressed M-bcr/abl transcripts, among whom 370 were in chronic phase (CP), and 109 in accelerated (AP)/blastic phase (BP). The percentages of patients with b2a2 transcripts in CP and AP/BP were 32.4% (120/370) and 36.7% (40/109) (P > 0.05). The b2a2 transcript patients in blastic crisis were 52.6% (10/19) for lymphoblastic and 33.3% (30/90) for myeloblastic (P > 0.05). The platelet count of untreated patients with b3a2 isoform [(485.9 +/- 333.8) x 10(9)/L, n = 125] was distinctly higher than those with b2a2 isoform [(380.5 +/- 321.9) x 10(9)/L, n = 62] (P < 0.05). 66.0% (31/47) and 64.4% (29/45) of the patients in CP and AP/BP respectively co-expressed M- and m-bcr/abl transcripts (P > 0.05). One patient expressed only m-bcr/abl transcript was of typical acute myeloblastic leukemia (AML). Both two micro -bcr/abl(+) patients were of typical CML.</p><p><b>CONCLUSIONS</b>Almost all typical CML patients express M-bcr/abl transcripts, most of them coexpress M-bcr/abl and m-bcr/abl transcripts, a few possesses only micro -bcr/abl fusion gene. m-bcr/abl(+) are usually associated with AML or CML in myeloblastic crisis besides acute lymphoblastic leukemia (ALL). Patients with b3a2 isoform are prone to higher platelet count before treatment.</p>

Follow-up detection of M-bcr/abl and m-bcr/abl fusion transcripts in chronic myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

In order to investigate the features of M-bcr/abl and m-bcr/abl fusion transcripts in patients with chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (SCT), M-bcr/abl and m-bcr/abl fusion transcripts were sequentially detected by RT-PCR technique in 72 CML patients after SCT. The results showed that M-bcr/abl positive rate (79.2%, 42/53) within 6 months after SCT was remarkably higher than that in 6-12 months group (34.3%, 11/32) and >or= 12 months group (35.1%, 13/37) (P < 0.001), and the clinical relapse rates in corresponding periods were 1.9% (1/53), 0% (0/32) and 16.2% (6/37) respectively. M-bcr/abl and m-bcr/abl fusion transcripts occurred in 5 of 6 clinically relapsed patients. In period of more than 6 months after transplantation, none of 17 M-bcr/abl(+) samples from 14 patients in cytogenetic remission appeared positive reaction of m-bcr/abl. It is concluded that M-bcr/abl(+) fusion transcript still existed in most patients after SCT, and usually disappeared within 6 months. Existence of M-bcr/abl is not a clinical relapse marker in CML patients. Simultaneous detection of M-bcr/abl and m-bcr/abl fusion transcripts can be helpful for monitoring residual disease.

Analysis of cytogenetic response in Ph+ chronic myeloid leukemia patients treated with interferon alpha / 中国实验血液学杂志

Ph chromosome occurs in nearly all patients with CML, and eliminating Ph-positive clone is a major target in the treatment of CML. IFN-alpha is a well-known effective treatment in chronic phase CML. The cytogenetic response and the prognostic factors in 128 CML patients treated with IFN-alpha were retrospectively studied. IFN-alpha administered singly at a dose of 3 million U/day for 2 - 3 times a week or in combination with either hydroxyurea (Hu), busulfan (Bu), low dose Ara-C or harringtonine. Karyotyping was examined by G-banding before and after IFN-alpha-based treatment. The results showed that all patients achieved complete hematological remission. Cytogenetic response occurred in 36 of 118 patients with standard t (9;22) translocation; 3 of these 36 patients had a complete cytogenetic response (Ph = 0), 13 had major cytogenetic responses (Ph < 35%) and 20 had minimal response (Ph > 35%). The total cytogenetic effectiveness was 13.6% (16/118). Four of seven patients with complicated variant translocation also achieved cytogenetic response, 2 of them had a major cytogenetic response and 2 had minimal response. Factors influenced the prognosis associated with cytogenetic response included sex, patient status at diagnosis and IFN-alpha administered singly or in combination with other chemotherapeutic agents. IFN-alpha could not prevent the progression of CML. It is concluded that Ph(+)CML patients with both standard and variant translocation had major cytogenetic response to IFN-alpha treatment at a dose of 6 - 9 million U/week in single or combination with Hu/Bu, however, IFN-alpha treatment could not prevent disease progression. Long term survival was also observed in patients with variant translocation treated with IFN-alpha. Regular cytogenesis examination in CML patients is necessary during IFN-alpha therapy, which is useful to reflect curative effect and progression of the disease.