| Objectives:1. To retrospective analyze the cytogenetic、clinical and laboratorial characteristicsof819hematological malignancy patients with chromosome1abnormality who wereenrolled at the department of hematology, affiliated No1hospital of SuzhouUniversity between January1,2000to June30,2012, which including417myeloidand312lymphoid hematological malignancies.2. To analyze the cytogenetic、clinical and laboratorial characteristics of30myeloid hematological malignancypatients with der(1;7)(q10;p10) abnormality, and investigate exon3,4,5,6,7regionmutation of RUNX1gene in23patients from their chromosomes suspension.Methods:1.819cases were confirmed with chromosome1mutation by R-band karyotypicanalysis using direct method and/or short-term culture for chromosomes preparation.These patients were classified into myeloid or lymphoid hematological malignancygroups and their cytogenetic、clinical and laboratorial characteristics were analyzed.2.We further analyzed the cytogenetic、clinical and laboratorial characteristics of30cases with der(1;7)(q10;p10) abnormality.23cases with well saved chromosomessuspension were chosen and exon3,4,5,6,7region mutation of RUNX1gene wereinvestigated by PCR amplification and following sequencing(assisted by ShanghaiYujing Biotech).Results:1. The cytogenetic and clinical characteristics of819hematologicalmalignancy patients with chromosome1abnormality, which including417myeloid and312lymphoid hematological malignancies (1) The cytogenetic and clinical characteristics of417myeloid hematologicalmalignancy patients with chromosome1abnormalityMales aged from30-69were dominant in these417myeloid hematologicalmalignancy patients. Among these patients,148cases were AML(35.5%),153wereMDS(36.7%),95were CML(22.8%) and21were MPN(5.0%).When analyzing the clinical and laboratorial characteristics according to differentdisease types, we found results as follows.1. Age of onset in descending order wasMPN, MDS,AML and CML. Compared with AML or CML, MPN and MDS weresignificantly elder dominant(P<0.05), which might relate with disease characteristics.2. No significant gender differences in the proportion of male and female patientswere found among these4disease types(P>0.05).3.Initial WBC count in descendingorder was CML, AML, MPN and MDS. There were significant differences betweenCML and AML、MPN or MDS, MPN and MDS, AML and MDS(P<0.05), whichmight relate with disease characteristics.4.Initial hemoglobin in descending order wasMPN,CML,AML and MDS. There were significant differences between MPN andCML、AML or MDS, CML and AML or MDS(P<0.05).5.Initial PLT count indescending order was MPN,CML,MDS and AML. There were significant differencesbetween MPN and MDS or AML, CML and MDS or AML(P<0.05).6.Medium lifespan in descending order was MPN,CML,MDS and AML. There were significantdifferences between MPN and MDS or AML, CML and MDS or AML, MDS andAML(P<0.05).When analyzing the clinical and laboratorial characteristics according to differentchromosome types which including+1、-1、1q trisome、del(1)、add(1)、inv(1)、t(1;v),no remarkable differences of onset age were found among all these groups, not weregender difference、WBC count、hemoglobin、PLT count or medium life span(P>0.05).Beside chromosome1, abnormalities could be involved in the other22chromosomes.The most common one occurred between the1st and the7th chromosomes, in which30cases were der (1;7)(q10; p10). Among the myeloid hematological malignancypatients with chromosomal1abnormality,115cases had1q trisomy (27.3%),95had t(1; v)(22.8%),46had+1(11.0%),40had del (1)(9.6%),36had add (1)(8.6%),15had inv(1)(3.6%),14had-1(3.4%) and the rest78had unclear location or rarekaryotype(19.2%). According to a detailed analysis of the various types of diseases, 1q trisome could be the most common karyotype in all myeloid diseases, while der (1)t (1; v)(q10; v) accounted for up to16.5%,+1, del (1), add (1) each about10%, inv (1)or-1was relatively rare(<5%). In all myeloid diseases,+1abnormality was mostcommonly found in CML patients(16/46,34.8%),-1abnormality was mostly commonin AML patients(7/14,50.0%),1q trisome abnormality was mostly common in MDSpatients(55/115,79.9%), del (1) abnormality was mostly common in MDSpatients(21/40,52.5%), add (1) was the most common abnormality in AMLpatients(15/36,41.7%), inv (1) was the most common abnormality in CMLpatients(7/15,46.7%), and t (1; v) was the most common abnormality in AMLpatients(34/95,35.8%). Myeloid hematological malignancy patients withchromosome1abnormality had poor prognosis. According to the numbers ofchromosomal abnormalities, Myeloid malignancy patients could be divided into threegroups including that with less than or equal3chromosomal abnormalities, more than3but less than or equal5chromosomal abnormalities and more than5chromosomalabnormalities. Medium life span in the group with less than or equal3chromosomalabnormalities was longer than that with more than5chromosomal abnormalities(P<0.05).(2) The cytogenetic and clinical characteristics of312lymphoid hematologicalmalignancy patients with chromosome1abnormalityYoung and middle aged males were dominant in these312lymphoidhematological malignancy patients. However,49more cases(15.7%) were childrenwhen compared with myeloid hematological malignancy patients. Among all theselymphoid hematological malignancy patients,151cases were ALL(48.4%),77wereMM/APCL(24.7%),54were NHL(17.3%),18were CLL(5.7%) and12wereMH(3.8%).When analyzing the clinical and laboratorial characteristics according to differentdisease types, we found results as follows.1. Age of onset in descending order wasCLL, MM/APCL, MH, NHL and ALL. There were significant differences betweenCLL and ALL or NHL, MM/APCL and NHL or ALL, MH and ALL, NHL and ALL(P<0.05).2. No significant gender differences in the proportion of male and femalepatients were found among all these disease types(P>0.05).3.Initial WBC count indescending order was CLL, ALL, NHL, MM/APCL and MH. There were significant differences between CLL and NHL、MM/APCL or MH(P<0.05).4.Initial hemoglobinin descending order was NHL, MH, CLL, ALL and MM/APCL.5.Initial PLT count indescending order was CLL, MM/APCL, NHL, ALL and MH. There were significantdifferences between CLL and NHL or ALL, MM/APCL and ALL or MH, NHL andALL or MH(P<0.05).6.Medium life span in descending order was CLL, MM/APCL,NHL, ALL and MH. There were significant differences between CLL andMM/APCL、NHL、ALL or MH, MM/APCL and MH, NHL and MH, ALL andMH(P<0.05).When analyzing the clinical and laboratorial characteristics according to differentchromosome types which including+1、-1、1q trisome、del(1)、add(1)、inv(1)、t(1;v),onset age in del(1) group was older than that in t(1;v) group, so was-1group(P<0.05).PLT count in del(1) group was higher than that in t(1;v) group, so was-1group(P<0.05). No remarkable differences of gender difference were found among allthese groups, not were WBC count、hemoglobin or medium life span(P>0.05). Besidechromosome1, abnormalities could be involved in the other22chromosomes. Themost common one occurred between the1st and the19th chromosomes, whichincluding der(19)t(1;19)(q23;p13) and t(1;19)(q23;p13). Among the lymphoidhematological malignancy patients with chromosomal1abnormality,83cases had1qtrisomy (26.6%),56had t (1; v)(17.9%),49had del (1)(15.7%),37had add (1)(11.9%),24had-1(7.7%),11had+1(3.5%),8had inv(1)(2.6%) and the rest59hadunclear location or rare karyotype(18.9%). According to a detailed analysis of thevarious types of diseases,1q trisome could be the most common karyotype in alllymphoid diseases, while der (1) t (1; v)(q?; v) accounted for up to13.5%, del (1)(p?)about9.0%, t(1;v)(q?;v) about11.2%,-1、+1or inv(1) was relatively rare(<5%). Inall lymphoid diseases,+1abnormality was most commonly found in ALLpatients(6/10,60.0%),-1abnormality was mostly common in MM/APCL patients(10/24,41.7%),1q trisome abnormality was mostly common in ALLpatients(44/83,53.0%), del (1) abnormality was mostly common in MM/APCLpatients(23/49,46.9%), add (1) was the most common abnormality in ALLpatients(19/37,51.4%), inv (1) was the most common abnormality in ALLpatients(5/8,62.5%), and t (1; v) was the most common abnormality in ALLpatients(45/56,80.4%). Lymphoid hematological malignancy patients with chromosome1abnormality had poor prognosis. According to the numbers ofchromosomal abnormalities, Iymphoid malignancy patients could be divided intothree groups including that with less than or equal3chromosomal abnormalities,more than3but less than or equal5chromosomal abnormalities and more than5chromosomal abnormalities. No significant difference was found in medium life spanamong three groups(P>0.05).2. Mutation analysis and clinical characteristics of30hematologicalmalignancy patients with der(1;7)(q10;p10) abnormalityIn these30cases,26cases were MDS(with7transformed to AML) and4caseswere AML. Their medium age was56.22males and8females were included.16patients had the sole abnormality as der (1;7)(q10; p10), while other14patientsaccompanied by der (1;7)(q10; p10) and other chromosomal abnormalities. Noremarkable differences of onset age were found between the up two groups, not weregender difference、WBC count、hemoglobin、PLT count or medium life span(P>0.05).23cases with well saved chromosomes suspension were detected by sequencinganalysis and2patients (2/23,8.7%) showed RUNX1gene mutation. In one patient(case15), the5th exon of RUNX1mutated from G to T. In the other patient (case22),the7th exon of RUNX1mutated from C to T. Case15patient with21months’ lifespan showed cytopenia in peripheral blood but no extramedullary infiltrationsymptoms such as lymph or organ enlargement. Case22patient with9months’ lifespan also showed cytopenia in peripheral blood but no extramedullary infiltrationsymptoms such as lymph or organ enlargement.Conclusions:1. In addition to the der (1;7)(q10;p10) in MDS, t (1;19)(q23; P13) in pre-ALLabnormal karyotype of chromosome1, the other is not special, visible to all kinds ofmyeloid and lymphoid malignancies. Chromosome1abnormality was commonlyinvolved in complex chromosome karyotypes and secondary abnormal, minority is theprimary exception. Medium life span in the myeloid malignancies that with less thanor equal3chromosomal abnormalities was longer than that with more than5chromosomal abnormalities(P <0.05). However, lymphoid hematological malignancypatients with chromosome1abnormality had poor prognosis, which had nothing to dowith the number of chromosomal abnormalities. 2. In myeloid hematological malignancy patients with chromosome1abnormality, the incidence of AML or MDS was significantly higher than that of MPN;and in lymphoid hematological malignancy patients with chromosome1abnormality,the incidence of ALL was significantly higher than other diseases.3. ALL with der(19)t(1;19)(q23;p13)/t(1;19)(q23;p13) abnormalities hadfollowing unique characteristics: they occurred commonly in children, adolescentsand younger adults, but, their occurrence had nothing to do with gender. They wereoften accompanied by other abnormalities besides der(19)t(1;19)(q23;p13)/(1;19)(q23;p13). When newly diagnosed, high WBC levels and extramedullary(liver,spleen, lymph nodes) infiltrations were commonly seen.4. MDS/AML with der(1;7)(q10;p10) abnormality had following uniquecharacteristics: males were dominant while peripheral PLT were lower in suchpatients and they had higher risks for leukemia transformations. No statisticaldifferences(P>0.05) were noticed in clinical and laboratorial information between thegroup with only der(1;7) abnormality and that accompanied by other chromosomalabnormalities.5. MDS patients with der(1;7)(q10;p10) abnormality and RUNX1gene mutationhad a trend of thrombocytopenia, short life survival and poor prognosis, whichdeserved more investigation. |
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