Chromosome Abnormalities and Their molecular Correlates in Acute Leukemia SALJUAN CHEN State Key laboratory of medical genomics Shanghai Institute of Hematology, Ruijin Hospital Shanghai Second Medical University(SsMU)
Chromosome Abnormalities and Their Molecular Correlates in Acute Leukemia SAI-JUAN CHEN State Key Laboratory of Medical Genomics Shanghai Institute of Hematology, Ruijin Hospital Shanghai Second Medical University(SSMU)
Development of Classification of Acute Leukemia 1976 French-American-British(FAB) Cooperative Group proposed classification of acute leukemia based on morphologic criteria that were subsequently refined in 1981 and 1985 1986 Morphologic, immunologic and cytogenetic (MIC) classification was introduced. Recognition of importance of cytogenetics in the diagnosis and treatment of acute leukemia 2001 World Health Organization(WHO) classification recognized new clinically relevant molecular genetic lesions
Development of Classification of Acute Leukemia 1976 French-American-British (FAB) Cooperative Group proposed classification of acute leukemia based on morphologic criteria that were subsequently refined in 1981 and 1985 1986 Morphologic, immunologic and cytogenetic (MIC) classification was introduced. Recognition of importance of cytogenetics in the diagnosis and treatment of acute leukemia 2001 World Health Organization (WHO) classification recognized new clinically relevant molecular genetic lesions
World Health Organization(WHO)Classification of Acute Leukemia with Corresponding FAB Classification Subtypes WHO classification" C ore esponding FAB subtypes Precursor lymphoblastic leukemia/lymphoblastic lymphoma Precursor B-cell acute lymphoblastic leukemia/lymphoma LI L2 Precursor T-lymphoblastic leukemia/lymphoblastic lymphoma LI L2 Burkitts lymphoma/leukemia Endemic Burkitt's lymphoma/leukemia Sporadic Burkitt's lymphoma/leukemia Immunodeficiency-associated Burkitt's lymphoma/leukemia 3 AML with recurrent genetic abnormalities AML with t(8: 21)( 22: 22): AMLl-ETO M2>MI>M4>MO AML wth abnormal marrow eosinophilia and inv(16)(p1 3q22)or t(16: 16)(p13: q22): CBFB-MYHll M4Eo>M4>M2>MI Acute promyelocytic leukemia with t(15: 17)(q22: q 12): PML-RARa M3>M2>MI AML with 11q23 abnormalities: MLL rearrangements M5>M4>M2>MI>MO AML with multilineage dysplasia Following a myelodysplastic syndrome or myeloproliferative disorder or without antecedent myelodysplastic syndrome M2>M4>M6 AML and myelodysplastic syndrome, therapy related Alkylating agent-related M2>M4>M6 Topoisomerase type II inhibitor-related M5>M4>M2>MI Other types AML not otherwise categorized Acute myeloid leukemia minimally differentiated Acute myeloid leukemia without maturation MI Acute myeloid leukemia with maturation M2 Acute myelomonocytic leukemia M4 Acute monoblastic leukemia 15 Acute erythroid leukemia Acute megakaryoblastic leukemia M7 Acute basophilic leukemia Acute panmyelosis with myelofibrosis M7:?MI: MDS Myeloid sarcoma Abbreviations: FAB, French-American-British: MDS, myelodysplastic syndrome. aFor details. see ref 6 bFor details, see refs. 3 and 4
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Acute leukemia of ambiguous lineage Undifferentiated acute leukemia CHLA-DR, CD34, CD38) Bilineal acute leukemia (dual population of blasts) Biphenotypic acute leukemia co-expression of myeloid and other lineage antigen)
Acute leukemia of ambiguous lineage • Undifferentiated acute leukemia (HLA-DR, CD34, CD38) • Bilineal acute leukemia (dual population of blasts) • Biphenotypic acute leukemia (co-expression of myeloid and other lineage antigen)
Major differences between WHO and FAB Replacing the morphologic terms of LI and L2 ALL with an immunologic classification consisting of precursor-B and precursor- t lymphoblastic leukemias that are further subgrouped by cytogenetic abnormalities Grouping L3 ALL with Burkitts lymphoma Lowering the blast count from 30 to 20% for the diagnosis of AML, with elimination of the myelodysplastic subgroup of refractory anemia with excess blasts in transformation RAEB-IT) Revision of the mds subdivision based on number of dysplastic lineages, presence of ringed sideroblasts, and blast percentage Recognition of distinct cytogenetic AML subtypes New category of AMl with multilineage dysplasia with or without an antecedent mds New category of Therapy-Related AML New category of Acute Leukemia of Ambiguous lineage Inclusion of a pure erythroid leukemia(M6b)in the AML Not Otherwise Categorized subgroup Recognition of the rare acute basophilic leukemia also in the AML Not Otherwise Categorized subgroup
Major differences between WHO and FAB