A Novel Karyotype in Acute Myeloid Leukemia with Basophilia

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, ?21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity.     

Bone marrow chromosomes in acute lymphoblastic leukaemia: A long-term study

The bone marrow chromosomes of 25 children with acute lymphoblastic leukaemia (ALL) were examined at diagnosis before treatment, during remission, and in 12 cases, also during relapse. Follow-up was for at least six years. At diagnosis, 17 patients had a major population of chromosomally abnormal cells and of these 11 had identifiable clones. The commonest abnormality was hyperdiploidy. Eight patients had predominantly normal cells, but four of these had a minor abnormal clone. In remission, some samples were completely normal but, when pooled, remission samples had a minor population of chromosomally aberrant cells which were rarely clonal. The incidence of structural abnormalities was the same in patients who ultimately relapsed and those who remained in first remission at the end of the study, but the presence of hyperdiploid cells and/or clones in remission was more frequently associated with subsequent relapse. Relapse patterns were of two kinds: in three patients there was a return of the chromosomal abnormalities seen at diagnosis; in six others, chromosomal features in relapse were distinct from those at diagnosis. It is suggested that relapse associated with distinct chromosomal features may represent malignant transformation of a previously unaffected cell line. While chromosomal abnormalities seen prior to treatment can be related to the leukaemic event alone, abnormalities seen in remission and in relapse may result partly from drug and X-ray treatment. The relative importance of treatment and other factors to chromosomal change in ALL is discussed.     

Acquired X-chromosome aneuploidy in children with acute lymphoblastic leukemia

BACKGROUND: A cytogenetic study of 75 consecutive children with ALL revealed a normal karyotype, a low hyperdiploid karyotype (including 47-50 chromosomes), and a high hyperdiploid karyotype (including > 50 chromosomes) in 10, 12, and 33 patients, respectively. An acquired extra X-chromosome was detected at diagnosis by conventional cytogenetics in 29 (88%) of 33 children with a high hyperdiploid karyotype and in 4 (33%) of 12 children with a low hyperdiploid karyotype. X-chromosome aneuploidy was retrospectively studied by fluorescence in situ hybridization (FISH) in eight and 20 patients with a normal and a hyperdiploid karyotype, respectively. PROCEDURE: A classical cytogenetic study was performed according to standard methods. FISH with the centromeric probe specific to X-chromosome was used to study interphase cells of bone marrow or blood samples. RESULTS: An extra X-chromosome was found by FISH in all 13 patients with a high hyperdiploid or tetraploid, in 6 of 7 patients with a low hyperdiploid, and in none with a normal karyotype. Two children with a normal karyotype displayed monosomy X. Altogether, 57.3% of newly diagnosed children displayed X-chromosome aneuploidy. CONCLUSIONS: Out study indicates that X-chromosome aneuploidy may be the most common chromosome abnormality in childhood ALL. It can be detected in nearly all children with a high hyperdiploid karyotype and up to one-half of the patients with a low hyperdiploid karyotype. FISH with an X-chromosome centromeric probe is a rapid and simple tool to detect an abnormal clone at diagnosis in the majority of children with ALL and is useful in confirming remission in these patients.     

Bone marrow chromosomes in acute lymphoblastic leukaemia: a long-term study.

The bone marrow chromosomes of 25 children with acute lymphoblastic leukaemia (ALL) were examined at diagnosis before treatment, during remission, and in 12 cases, also during relapse. Follow-up was for at least six years. At diagnosis, 17 patients had a major population of chromosomally abnormal cells and of these 11 had identifiable clones. The commonest abnormality was hyperdiploidy. Eight patients had predominantly normal cells, but four of these had a minor abnormal clone. In remission, some samples were completely normal but, when pooled, remission samples had a minor population of chromosomally aberrant cells which were rarely clonal. The incidence of structural abnormalities was the same in patients who ultimately relapsed and those who remained in first remission at the end of the study, but the presence of hyperdiploid cells and/or clones in remission was more frequently associated with subsequent relapse. Relapse patterns were of two kinds: in three patients there was a return of the chromosomal abnormalities seen at diagnosis; in six others, chromosomal features in relapse were distinct from those at diagnosis. It is suggested that relapse associated with distinct chromosomal features may represent malignant transformation of a previously unaffected cell line. While chromosomal abnormalities seen prior to treatment can be related to the leukaemic event alone, abnormalities seen in remission and in relapse may result partly from drug and X-ray treatment. The relative importance of treatment and other factors to chromosomal change in ALL is discussed.     

Unusual inclusions in mature polymorphonuclear neutrophils of cyclic neutropenia

The bone marrow of an 11-year-old girl with cyclic neutropenia was examined by electron microscopy. In the nonneutropenic phase, mature polymorphonuclear neutrophils had numerous bundles of filamentous inclusions in both cytoplasms and nucleus. Primary granules were slightly increased in number. Similar filament-like inclusions also have been reported in some cases of hemopoietic dysplasia; however, our case showed no abnormality in chromosomes, no thrombocytopenia, and no leukemic change.     

儿童近四倍体急性髓系白血病的实验室研究

近四倍体在儿童髓系恶性肿瘤中是一种少见的遗传学异常,其意义还不清楚。该文就1例近四倍体的儿童急性髓系白血病（AML-M4）分析其特点。采用骨髓涂片方法分析骨髓细胞形态,收集骨髓标本做流式细胞术分析,24 h培养R显带做常规核型分析。该病例骨髓细胞形态学分析显示大而突出的胞核,染色体分析显示近四倍体核型,结合骨髓形态和免疫分型结果诊断为AML-M4。患儿经过4个疗程的化疗治疗,最终获得了临床缓解, 但该患儿达到缓解的时间比正常核型患儿要长。我们认为近四倍体核型是影响儿童AML治疗与预后的重要因素。［中国当代儿科杂志,2009,11（4）：263-266］     

AGAMMAGLOBULINEMIA ASSOCIATED WITH THE OCCURRENCE OF A MONOCLONAL IMMUNOGLOBULIN

Abstract. A patient is described with a monoclonal immunoglobulin of the IgG class in the serum and no detectable IgM and IgA. Extensive immunological investigations showed the absence of B-lymphocytes in bone marrow and peripheral blood. Moreover, plasma cells were not present in the bone marrow. The monoclonal IgG was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was normal. Clinically the patient suffered from gastrointestinal and severe respiratory tract infections. It was concluded that the findings are consistent with the diagnosis congenital agammaglobulinaemia with concurrence of monoclonal IgG. It was postulated that the cell clone in the gastrointestinal tract resulted from an escape of a pre-B cell clone from the recognized arrest of pre-B cells in congenital agammaglobulinaemia.     

Agammaglobulinaemia associated with the occurrence of a monoclonal immunoglobulin.

A patient is described with a monoclonal immunoglobulin of the IgG class in the serum and no detectable IgM and IgA. Extensive immunological investigations showed the absence of B-lymphocytes in bone marrow and peripheral blood. Moreover, plasma cells were not present in the bone marrow. The monoclonal IgG was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was normal. Clinically the patient suffered from gastrointestinal and severe respiratory tract infections. It was concluded that the findings are consistent with the diagnosis congenital agammaglobulinaemia with concurrence of monoclonal IgG. It was postulated that the cell clone in the gastrointestinal tract resulted from an escape of a pre-B cell clone from the recongized arrest of pre-B cells in congenital agammaglobulinaemia.     

Juvenile chronic myelogenous leukemia: surface antigen phenotyping by monoclonal antibodies and cytogenetic studies

Cells from three children with juvenile chronic myelogenous leukemia were studied using culture in semisolid media, cytogenetic analysis, and surface staining with the monocyte-specific monoclonal antibodies 61D3 and 63D3. The percentage of bone marrow mononuclear cells that were 61D3- and 63D3-positive was markedly increased in all three patients. Bone marrow and peripheral blood mononuclear cells exhibited exceptionally bright immunofluorescence with these antibodies. The presence of monocyte-specific antigens on the surface of juvenile chronic myelogenous leukemia cells suggests that they are derived from a precursor with monocytic characteristics. A specific chromosomal abnormality (47,XY+21) was present in fresh bone marrow cells from one patient; in contrast, 50 metaphases from phytohemagglutinin-stimulated peripheral blood contained a normal karyotype. The chromosomal abnormality was also identified in myeloid colonies grown in vitro from this patient. Granulocytic elements were demonstrated in tissue sections and in cultured myeloid colonies from this child. Our data suggest that malignant transformation in juvenile chronic myelogenous leukemia involves a myeloid progenitor population capable of differentiation in vitro to cells with monocytic or granulocytic characteristics.     

Acute megakaryoblastic leukemia in Down's syndrome: report of a case and review of cytogenetic findings

A case of a child with trisomy 21 and acute megakaryoblastic leukemia (AMBL) is reported. Histological examination of the bone marrow showed progressive fibrosis and replacement with megakaryoblasts. The diagnosis was confirmed by platelet peroxidase reaction and immunofluorescent staining with anti-factor VIII. Serial cytogenetic studies using banding techniques at various stages during the course of the disease (preleukemia, leukemia, remission, and relapse) showed several chromosomal abnormalities (unbalanced translocation between chromosomes 1 and 4 leading to trisomy 1q, trisomy 7q, monosomy 7p, and a reciprocal translocation between chromosomes 10 and 16). AMBL in childhood is probably more common than previously reported. Any association between AMBL and a particular cytogenetic abnormality must await further cytogenetic studies, specifically those employing banding techniques.     

Severe congenital leukopenia (reticular dysgenesis). Immunologic and morphologic characterizations of leukocytes

We report fatal reticular dysgenesis in a premature infant presenting with severely decreased blood and bone marrow granulocytes and lymphocytes, an absent thymic shadow by x-ray film, and generalized lymphoid hypoplasia. Immunologic and electron microscopic evaluation of his white blood cells demonstrated that, despite extremely low cell numbers, cells from all stages of both granulocytic and lymphocytic development were present. Immature bone marrow cells of both myeloid and lymphoid lineages were found in much greater proportions than were mature cells; pre-B cells outnumbered B cells by more than tenfold. Megakaryocytes and erythroid cells appeared to be present in normal numbers, and tritiated-thymidine incorporation by bone marrow nucleated cells was also normal, although it may have largely occurred in erythroblasts. These data suggest that the primary defect in reticular dysgenesis is not failure in initiation of stem cell differentiation along lymphoid and myelomonocytic lines but rather an, as yet, undefined abnormality that interferes with normal growth and maturation of immune cells committed to these differentiation pathways.     

The multiple hematologic manifestations of neuroblastoma

The hematologic manifestations of neuroblastoma are numerous and varied. Bone marrow invasion by tumor cells may cause leukoerythroblastic changes or depression of one or more of the cell lines in the peripheral blood; occasionally bone marrow involvement may be so extensive that tumor cells may be released into the peripheral blood and lead to an erroneous diagnosis of leukemia. Anemia in neuroblastoma patients may result not only from bone marrow involvement, but also from bleeding into a tumor mass or from the hemolysis accompanying a consumption coagulopathy. A specific morphologic abnormality, the cogwheel erythrocyte, has been reported in patients with neuroblastoma. Neuroblastoma may also be associated with elevation of the platelet count or a hypercoagulable state. Recognition of these protean hematologic manifestations may facilitate diagnosis in children with atypical presentations of this highly malignant tumor.     

Leukemic xanthomatosis with a missing No. 9 chromosome

A 2 year old girl with chronic rhinobronchitis, hepatomegaly, café-aulait spots, skin xanthomas, mental and physical retardation and a blood picture of myelocytic leukemia is described. Treatment with prednisone and 6-mercaptopurine markedly improved the symptoms. The atypical cells could be classified as (para)metayelocytes by light and electron microscopic cytochemistry. Chromosome analysis of blood and bone marrow revealed a predominant cell clone in the bone marrow with a missing C-chromosome. The missing chromosome could be identified as a No. 9 by a modified Giemsa banding technique.Supported by the Deutsche Forschungsgemeinschaft.     

Prognostic impact of bone marrow karyotype in childhood acute lymphoblastic leukaemia: Swedish experiences 1986-91

Abstract The prognostic value of cytogenetic classification in acute lymphoblastic leukaemia (ALL) was evaluated in Swedish children below 16 years of age ( n = 372) diagnosed between 1986 and 1991. A bone marrow karyotype was obtained in 281 cases, of which 149 (53%) showed clonal abnormalities. Event-free survival (p-EFS) was 0.64–0.69 in patients with diploid and pseudodiploid karyotype. Patients with massive hyperdiploidy (> 50 chromosomes) had the best outcome (p-EFS = 0.76) and those with hypodiploidy (< 46 chromosomes) had the worst (p-EFS = 0.33). White blood cell count and age were the strongest predictors of outcome. The karyotype reached borderline significance. The diagnostic karyotype was also a predictor of outcome after relapse, with hyperdiploid patients doing better than the others. The presence of a structural chromosomal abnormality did not constitute a negative prognostic factor when intensive chemotherapy was given.     

Childhood myelodysplastic syndromes: Clinical features,cytogenetics and prognosis

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominence. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominence of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy.     

Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome

Shwachman Diamond syndrome (SDS) is a genetic disorder characterized by pancreatic hypoplasia, recurrent infection and bone marrow dysfunction. Some cases have an abnormality of chromosome 7, such as isochromosome 7q (i(7q)), which may be associated with the development of leukemia. We present a boy who was diagnosed with SDS at 19 months of age. From age 5-14 years, bone marrow cytogenetics has shown a consistent abnormality - i(7q), with an intermittent separate abnormality - deletion 20q, from age 11 years. During this time, the boy has been clinically well without leukemic signs, managed conservatively. We suggest that deletion 20q may be a non random secondary change in SDS with i(7q).     

CLONAL MONOSOMY 7 AND 5q IN A CHILD WITH MYELODYSPLASTIC SYNDROME

The authors report the case of a 5-year-old boy referred for thrombocytopenia and neutropenia. Bone marrow examination showed a myelodysplasia with clonal monosomy7. The acceleration of the disease was marked by the appearance of an additional cytogenetic abnormality, i.e., the deletion of the long arm of chromosome 5 in the clonal cells. RAS genemutationwas not detected. Chemotherapy was started to achieve complete remission before a bone marrow transplatation. This treatment was complicated by a prolonged a plasia and the patient died of systemic mycotic infection.     

Clonal monosomy 7 and 5q--in a child with myelodysplastic syndrome

The authors report the case of a 5-year-old boy referred for thrombocytopenia and neutropenia. Bone marrow examination showed a myelodysplasia with clonal monosomy7. The acceleration of the disease was marked by the appearance of an additional cytogenetic abnormality, i.e., the deletion of the long arm of chromosome 5 in the clonal cells. RAS genemutationwas not detected. Chemotherapy was started to achieve complete remission before a bone marrow transplatation. This treatment was complicated by a prolonged a plasia and the patient died of systemic mycotic infection.     

再生障碍性贫血患儿骨髓间充质干细胞体外造血支持作用的研究

目的：骨髓间充质干细胞（mesenchymal stem cell, MSC）具有造血支持作用，再生障碍性贫血（aplastic anemia, AA）的发病机制涉及到造血微环境的异常，将两方面联系起来，体外研究再障患儿骨髓MSC的造血支持作用与再障的造血微环境异常的关系。方法：采集24例再障患儿和19例对照儿童的骨髓标本，分离、培养和扩增MSC；观察细胞形态及骨髓MSC成纤维细胞集落形成单位（CFU-F）计数分析；应用MTT法检测骨髓MSC粘附造血细胞的能力；应用ELISA检测骨髓MSC分泌干细胞生长因子（SCF）的浓度；对骨髓MSC进行贴壁培养，接种骨髓单个核细胞，计数扩增细胞数和红系爆式集落生成单位（BFU-E），粒细胞巨噬细胞集落生成单位（CFU-GM），混合细胞集落生成单位（CFU-GMME）。结果：①再障患儿骨髓MSC传代时间延长，CFU-F计数15.70±5.78显著低于对照组21.73±5.74，P<0.05；②再障患儿骨髓MSC培养上清中SCF的浓度30.69±16.82 pg/mL显著低于对照组50.74±14.83 pg/mL，P<0.01；③再障患儿骨髓MSC支持下的单个核细胞（MNC）细胞扩增总数和红系爆式集落生成单位（BFU-E），粒细胞巨噬细胞集落生成单位（CFU-GM），混合细胞集落生成单位（CFU-GMME）计数显著低于对照组，P<0.01。结论： 再障患儿骨髓MSC体外造血支持作用较对照儿童骨髓MSC显著降低，其发生机制可能与再障患儿骨髓MSC增殖能力减低及分泌SCF减少有关。     

INTERMITTENT 20q- AND CONSISTENT i(7q) IN A PATIENT WITH SHWACHMAN-DIAMOND SYNDROME

Shwachman Diamond syndrome (SDS) is a genetic disorder characterized by pancreatic hypoplasia, recurrent infection and bone marrow dysfunction. Some cases have an abnormality of chromosome 7, such as isochromosome 7q (i(7q)), which may be associated with the development of leukemia. We present a boy who was diagnosed with SDS at 19 months of age. From age 5-14 years, bone marrow cytogenetics has shown a consistent abnormality - i(7q), with an intermittent separate abnormality - deletion 20q, from age 11 years. During this time, the boy has been clinically well without leukemic signs, managed conservatively. We suggest that deletion 20q may be a non random secondary change in SDS with i(7q).