Page 414 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

398 PART 6 ■ Neoplastic Disorders

m A AML

x . m m CD ,

- j
Donor Graft and Cell Source Options ( -CD CD ). CD -

A HLA-m . G m .

HLA-m m . S

, m HLA-m NOTE: This is a good time to complete Review Questions

q m . related to this content.

Com plications of Allotransplantation

A m - , k m - ACU E LYMPHOBLAS IC LEUKEMIA

, - , m ,

m . L m k Epidemiology

GVHD

. N k m I U S , ALL m mm -

m , % m

m . . I , -

A GVHD m j z U S .

. Ex mm ALL m , k

m k , x m ,

E -B m - . P ALL m

k m . (m : m , %: %). T

ALL .

New Therapies T . /m H , .

/m , . /m k .
N m m AML( . ) -

Pathogenesis

k ,

DNA m , x , - S D ’ m -

x m , m - k ALL, m

, k m m - . z . S q q

I m ALL

k , - ( . ).

m m z m IDH IDH , M m -

q m AML - , ARID B, CEBPE, GA A1,

. N m x IKZF , k ALL -

. ALL . R m- m PAX5

Proposed Sequential Acquisition of Genetic Alterations Contributing to Pathogenesis
TABLE 21.14
of ALL

Stage Impacted Cells Comments

Predisposition Hematopoietic stem cells Common variants—IKZF1, CEBPE, ARID5B

Created by either common inherited variants or, Rare mutations PAXS, ETV6, TP53
rarely, deleterious germ-line mutations.

Initiating Translocation Lymphoid progenitor Self-renewal, developmental arrest,

Lesions are acquired. epigenetic reprogramming, proliferation

Secondary Mutations Pro-B or pre-B cell Tumor suppressors, Kinase-Ras-P13K

Along with structural genetic alterations signaling, lymphoid signaling, tran-
contribute to an arrest in lymphoid development scriptional coactivators, chromatin

and disruption of multiple cellular pathways remodeling

Diagnosis Lymphoblasts

Modi ed from Hunger SP, Mullighan CG, Acute lymphoblastic leukemia in children, N Engl J Med, 373(16), 1541–1552, 2015.