1?Genetic Changes In RARA-rearrangement Negative Acute Leukemia With Promyelocytic Differentiation;2?Ph+ Acute Myeloid Leukemia With Masses And Osteolytic Lesions:finding Of PET/CT

Acute promyelocytic leukemia(APL)is currently the most widely studied,the most in-depth and most effective type of acute myeloid leukemia.The clarification of the genetic and molecular biology of the disease is also the most thorough.The RARA gene on chromosome 17 undergoes rearrangement of the RARA gene,and the combination of X-RARA(X represents a series of partner genes)with other genes is the most important driver gene mutation of APL.The most common reproducible chromosomal abnormalities are chromosome 15 and 17 translocations,t(15;17)(q22;q12-23),accounting for approximately 95%-98%of all cases of acute promyelocytic leukemia.The result of this translocation is the recombination of the PML and RARa genes to produce the PML-RARa fusion gene.As the drug that specifically targets this fusion gene,the appearance of all-trans retinoic acid and arsenious acid caused a reversible change in the prognosis of the disease.However,there are a few cases of acute myeloid leukemia whose cytomorphology,immunology and even clinical manifestations resemble those of acute promyelocytic leukemia,but no RARA fusion gene was detected.This type of leukemia is also known as acute promyelocytic-like leukemia(APLL).Its classification is also uncertain,some authors have classified it as acute myeloid leukemia M2 type(FAB classification).For many years,the molecular biology of APLL has remained unclear.Retinoic acid receptors(RARs)are a subfamily of Nuclear Receptor Superfamily,including three subtypes of RARA,RARB and RARG.These three subtypes are highly conserved in evolution,and their sequences and functions are highly similar.Retinoic X receptors(RARs),another subfamily of nuclear receptor superfamily,are also highly conserved,and their sequences are similar to RARs.Moreover,RXRs are closely related to the function of RARs,and they need to form heterodimers to function together.Therefore,researchers had speculated that RARB and RARG may play an important role in RARA fusion gene-negative APLL.After entering the 21st century,with the development of science and technology,a variety of hiRh-throughput detection technologies are in the ascendant and become a powerful research tool for genomics research.Many disease genetic abnormalities can be discovered.In recent years,the recurrent RARB and RARG fusion genes were found in the APLL,and previous researchers' conjecture was verified.However,there are also patients with promyelocytic leukemia that do not have fusion genes of RAR family members.The above description of the heterogeneity of the APLL genome abnormalities also suggests that researchers are concerned about the abnormality of RARs in promyelocytic acute leukemia.Due to the relatively low incidence of APLL and the emergence of new research techniques,the molecular pathology of APLL is still in its infancy.In this study,transcriptome sequencing was used to detect promyelocytic acute leukemia and to detect abnormal mRNA levels,especially RARs and RXRs.Objective:Detection of promyelocytic differentiation of acute leukemia,to find abnormal mRNA levels.Explore new gene mutations including RARs,RXRs family members,fusion genes and transcripts to elucidate the molecular pathology of this disease.Materials and Methods:The bone marrow samples of 4 patients with acute leukemia differentiated from promyelocytic leukemia were selected and mononuclear cells were extracted.RNA was extracted and a cDNA library was constructed;second-generation sequencing;bioinformatics analysis.RT-PCR and PCR,Sanger sequencing to verify transcriptome sequencing results.The AML data of the TCGA database was download to compare and analyze the transcriptome expression profile with the experimental specimensResults:New fusion genes were detected in each case,but none of the fusion genes of RARs or RXRs were found.A new transcript of the RXRA gene was detected in one caseRARA and RARB gene transcripts were detected in 1 case.A new RARB gene transcript was detected in 1 case.The comparison with the TCGA-LAML database showed that the expression profile of the case group was different from the classic M3 or non-M3 group,showing its uniquenessConclusions:In promyelocytic-differenting acute leukemia without RARA rearrangement,a series of novel fusion genes were found,and novel transcripts of the RARA,RARB and RXRA genes were detected.The cases owned unique gene expression profile characteristicsThe Philadelphia chromosome positive acute myelogenous leukemia(AML)is a type of controversial leukemia,which is characterized by the clinical features of acute leukemia.Whether this type of leukemia is a primary acute leukemia or the blast crisis of chronic myeloid leukemia has long been unresolved.Until recently,studies have found that such diseases may have molecular biological abnomialities different from acute granulocyte leukemia,and the 2016 WHO lymphatic hematopoietic tumor classification(fourth revision)lists them as separate classifications.However,the current research evidence is still insufficient,so WHO only uses Ph+ acute myeloid leukemia as a tentative type.Unlike solid tumors,soft tissue masses or bone destruction arc extremely rare in leukemia.These two types of phenomena are scattered in the literature,usually a single tumor or bone destruction,and appear alone.None of the two reported cases of Ph t AML have been reported.We have found a case of patients with Ph+ AML in the clinic,which has multiple soft tissue masses and multiple bone destruction.This phenomenon is reported for the first time.The chemotherapy response is also poor,the survival time is short,showing a poor prognosis.PET(Positron emission tomography)/CT has become the most effective means for tumor diagnosis and guidance treatment.In the field of hematological oncology,PET/CT is mainly used for the diagnosis and treatment of lymphoma,but less for leukemia examination.In this part of the study,we reported the use of PET / CT as a means of development,giving full play to its detection advantages.Objective:This study demonstrates the PET/CT features of Ph+ AML with multiple tumors and osteolytic lesions;and explores the differential diagnosis of Ph+ acute myeloid leukemia as a possible disease entity and chronic myeloid leukemia.Materials and Methods:A newly diagnosed patient with Pli+ acute myeloid leukemia admitted to the Affiliated Hospital of Qingdao University was enrolled in the study.Peripheral blood mononuclear cells(PBMCs)were isolated by Ficoll density gradient centrifugation.Karyotype analysis was performed;RT-PCR was used to detect BCR-ABL fusion gene mRNA expression;Sanger sequencing confirmed the base sequence of BCR-ABL fusion gene.18F-FDG PET/CT imaging confirmed systemic tumor infiltration.Results:1.The history of the patient is traced,the patient is in acute pathogenesis and has a poor prognosis.2.Karyotype analysis revealed the presence of the Ph chromosome.RT-PCR and Sanger sequencing analysis confirmed the presence of the BCR-ABL fusion gene without mutation.3.18F-FDG PET/CT showed high metabolism in the bone marrow,liver and spleen;there were multiple osteolytic lesions and soft tissue masses.Conclusions:1.Ph+ acute myeloid leukemia has certain clinical uniqueness and may be an independent disease entity,which needs further research to further clarify.2.For the first time,cases of multiple tumors and bone destruction in acute leukemia were reported.