B ALL | Anatomy2Medicine
Acute Leukemia Adults

B ALL

    • Acute Lymphoblastic Leukemia/Lymphoma
    • neoplasms composed of immature B (pre-B) or T (pre-T) cells, which are referred to as lymphoblasts
    • About 85% are B-ALLs, which typically manifest as childhood acute “leukemias.”;
    • T-ALLs tend to present in adolescent males as thymic “lymphomas.”(MCQ)
    • ALL is the most common cancer of children.
    • slightly more frequent in boys than in girls
    • B-ALL peaks in incidence at about the age of 3
  • peak incidence of T-ALL is in adolescence
  • Morphology.
      • In leukemic presentations, the marrow
        • hypercellular
        • packed with lymphoblasts, which replace the normal marrow elements.
  • T-ALLs
        • Mediastinal thymic masses occur in 50% to 70% (MCQ)
        • more likely to be associated with lymphadenopathy and splenomegaly
      • myeloblasts vs lymphoblasts
        • lymphoblasts (MCQ)
          • have more condensed chromatin
          • less conspicuous nucleoli
          • smaller amounts of cytoplasm that usually lacks granules.
          • myeloperoxidase-negative
          • often contain periodic acid–Schiff-positive cytoplasmic material
  • Immunophenotype
  • Immunostaining is done for terminal deoxynucleotidyl-transferase (TdT) (MCQ)
        • a specialized DNA polymerase (MCQ)
        • it  is expressed only in pre-B and pre-T lymphoblasts
        • is positive in more than 95% of cases
      • B-ALL vs  T-ALLs
  • B-ALLs
          • In most of B-ALLs  lymphoblasts usually express the(MCQ)
  • pan B-cell marker CD19
  • transcription factor PAX5
  • CD10.
  • In very immature B-ALLs (MCQ)
  • CD10 is negative
    • more mature “late pre-B” ALLs express (MCQ)
  • CD10, CD19, CD20
  • cytoplasmic IgM heavy chain (μ chain).
  • T-ALLs
        • In most cases of T-ALLs  the cells are positive for (MCQ)
          • CD1, CD2, CD5, and CD7
        • The more immature tumors are usually negative for (MCQ)
  • surface CD3, CD4, and CD8
        • “late” pre-T cell tumors are positive for (MCQ)
  • surface CD3, CD4, and CD8
  • Molecular Pathogenesis.
      • Approximately 90% of ALLs have numerical or structural chromosomal changes.
  • Most common is hyperploidy (>50 chromosomes) (MCQ)
        • hyperdiploidy and hypodiploidy are seen only in B-ALL.
      • Many of the chromosomal aberrations seen in ALL dysregulate the expression and function of transcription factors that are required for normal B- and T-cell development.
  • NOTCH1 gene(MCQ)
          • Up to 70% of T-ALLs have gain-of-function mutations in NOTCH1
          • NOTCH1 is a gene that is essential for T-cell development.
        • a high fraction of B-ALLs have
          • loss-of-function mutations in genes that are required for B-cell development, such as PAX5, E2A, and EBF (MCQ)
          • a balanced t(12;21) involving the genes TEL and AML1, two genes that are needed in very early hematopoietic precursors. (MCQ)
        • All of these varied mutations seem to disturb the differentiation of lymphoid precursors and promote maturation arrest
  • Clinical Features of ALL
      • Abrupt stormy onset within days to a few weeks of the first symptoms
      • Symptoms related to depression of marrow function
      • Mass effects caused by neoplastic infiltration
        • bone pain resulting from marrow expansion and infiltration of the subperiosteum
  • generalized lymphadenopathy
  • splenomegaly, and hepatomegaly
  • testicular enlargement
  • in T-ALL, complications related to compression of large vessels and airways in the mediastinum(MCQ)
      • Central nervous system manifestations
        • headache, vomiting
        • nerve palsies resulting from meningeal spread
  • Prognosis. (A Very Very High yield topic for MD Entrance, MBBS Exams, USMLE)
      • Pediatric ALL is one of the great success stories of oncology
      • With aggressive chemotherapy
        • about 95% of children with ALL obtain a complete remission(MCQ)
        • 75% to 85% are cured
  • Factors consistently associated with a worse prognosis(MCQ)
        • age under 2, (MCQ)
  • largely because of the strong association of infantile ALL with translocations involving the MLL gene
  • presentation in adolescence or adulthood;
        • peripheral blood blast counts greater than 100,000
          • reflects a high tumor burden
        • the presence of particular cytogenetic aberrations such as the t(9;22) (the Philadelphia chromosome) (MCQ)
  • t(9;22) is present in only 3% of childhood ALL, but up to 25% of adult cases
      • Favorable prognostic markers include
        • an age of 2 to 10 years
        • a low white cell count
  • hyperploidy(MCQ)
      • trisomy of chromosomes 4, 7, and 10, (MCQ)
      • the presence of a t(12;21) (MCQ)
      • the molecular detection of residual disease after therapy is predictive of a worse outcome in both B- and T-ALL
    • BCR-ABL-positive B-ALL
      • generates mutations at a high rate, a phenomenon referred to as genomic instability (MCQ)

contributes to the clinical progression and therapeutic resistance of many aggressive malignant tumors.