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Hematologic malignancies share the common characteristic that they arise from ______ ____ that came from a transformed cell of marrow derivation

clonal populations



malignancy of hematopoetic cells, where the chief manifestation is involvement of the blood and marrow



a malignancy of hematopoetic cells, derived from lymphocytes or their precursors, which presents primarily as a solid mass


Extramedullary myeloid tumor

(granulocytic sarcoma)-a malignancy of hemaotpoetic cells, derived from myeloid cells or their precursors (granulocytes, monocytes, etc) which presents primarily as a solid mass


Persistant findings of chromosomal translocation are important to note because:

1) their persistence allows them to be used as diagnostic markers for certain hematological malignancies
2) Their persistent presence suggests they play critical role in development of the hematological malignancy they are associated with


What might be one explanation of the frequent translocations in lymphocytes?

genomic instability during immunoglobulin/T cell receptor rearrangement in B and T cells


3 viruses known to play a role in lymphomas:

1) Epstein-Barr virus (EBV)
2) Human T cell leukemia virus-1 (HTLV-1)
3)Kaposi sarcoma herpesvirus/Human herpesvirus-8 (KSV/HHV-8)


Acute Leukemias

Usually due to rapid accumulation of (usually) immature cells in the marrow. They often replace many normal marrow cells, resulting in cytopenias. Most can be classified as Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia


Myelodysplastic syndromes

a group of conditions where a clonal population derived from a neoplastic HSC takes over marrow, and is NOT capable of making normal blood cells in one or more lineages (dysplasia). Categorized by falling peripheral blood cell counts. Often MDS can progress to AML


Myeloproliferative Neoplasms

neoplastic clonal proliferations of the marrow where the clone makes normal functioning blood cells, usually in multiple lineages, but makes too many of them in one or more lineages.


What causes the signs and symptoms of acute leukemia?

When immature leukemic cells accumulate in the bone marrow, they displace normal hematopoetic elements.


Chromosomal abnormalities may be found in __% of AML patients and ___% of ALL patients



Different types of AML:

granulocytic, monocytic, erythroid, megakaryocytic


Risk factors for acute leukemia

-previous chemo, esp. with DNA alkylating agents and topoisomerase II inhibitors
-tobaccos smoke
-ionizing radiation
-benzene exposure
-Syndromes: Down, Bloom, Fanconi anemia, ataxia-telangiectasia


Signs and symptoms of acute leukemia

fatigue, malaise, dyspnea, easy bruisability, weight loss, bone pain, anemia and pallor, thrombocytopenia, hemorrhage, ecchymoses, petechia, fundal hemorrhage, fever and infection, adenopathy, hepatosplenomegaly, mediastinal mass


Most common age for ALL

75% of cases of ALL occur in children under age 6


In order to diagnose ALL, lymphoblasts must be identified. This is done with :



Immunophenotyping markers to diagnose ALL

CD34-marks immature lymphobasts, but often expressed by myloblasts.
TdT-expressed by immature lymphocytes only


Does B-ALL or T-ALL account for more cases of ALL?

B-ALL accounts for 80-85% of all cases of ALL


B lymphoblasts express Be lineage antigens:

CD19, CD22, CD79a
usually do not express mature B cell markers such as CD20


Recurrent cytogenetic abnormalities of B-ALL

1) t(9,22) BCR-ABL1
2) t of 11q23, MLL
3) t(12;21) ETV6-RUNX1


Rank the prognoses of the most common B-ALL cytogenetic abnormalities

t(12;21) > t 11q23 MLL > t(9;22)


What age group does T-ALL occur in most commonly?

adolescents and young adults and males more than females


How does T-ALL often present?

with a component of lymphoblastic lymphoma (T-LBL), often manifesting as a large mediastinal mass


T lymphoblasts express T-lineage antigens ___, ___, and/or ____. They may express both ___ and ___ concurrently, or may express just one/neither. They often express T-lineage antigens only seen in immature T cells, such as ____and ___

CD2, CD3, CD7
CD4, CD8
CD99, CD!a


What is the prognosis for ALL in children? In adults?

Good prognosis in children, complete remission rate 95%, 80% cure rate. In adults, disease is much worse. Complete remission 60-80%, cure rate of <50%


Prognostic factors for all ALLs

Age (worst for infants, >10)
WBC count (more=worse)
Slow response to therapy, disease left after treatment
hyperdiploidy=good, hypodiploidy=bad
T cell worse


Who does AML occur in most commonly?

average age id 65, rare in children and young adults


the diagnosis of AML is usually based on:

identifications of increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood. (exception: if one can document presence of Auer rods)


Auer rods

Indicate AML and are found in myeloblast